Composition for preventing solidification and method for improving flow characteristics of hygroscopic tin salts

Abstract

The present disclosure generally relates to a particulate composition comprising a source of stannous particles, alumina, and a drying aid. The present disclosure further relates to a method for improving the flowability of particulate stannous particles by mixing alumina and a drying aid with the particulate stannous particles, thereby imparting improved flow characteristics to stannous chloride.

Description

Technical Field

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 368,067, filed Jul. 11, 2022, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates to a particulate composition comprising a particulate source of stannous, alumina, and a drying aid. The technology further relates to a method of improving the flowability of particulate stannous by mixing alumina and a drying aid with particulate stannous, thereby imparting improved flow characteristics to stannous chloride.

Background Art

[0003] Stannous (stannous) ions provided in oral compositions by stannous chloride and / or other stannous salts have long been evaluated for the multiple benefits they can provide, including antibacterial effects, control of bad breath, control of plaque growth and metabolism, reduction of gingivitis, reduction of progression to periodontal disease, reduction of dentin hypersensitivity, and reduction of coronal and root caries and erosion.

[0004] The use of stannous salts as raw materials can cause problems. For example, both the dihydrate and anhydrous forms of stannous chloride are hygroscopic materials and thus attract water vapor from the air by both absorption and adsorption. This makes the powder compound sticky. The particles can bind together, but aggregates may form during transportation and storage, thus causing difficulties in flowability during processing. Hygroscopic materials also tend to become wet and soft over time when exposed to air containing a large amount of moisture. Therefore, the moisture levels retained by these hygroscopic salts usually are proportional to the humidity levels.

[0005] Transporting, storing, and handling stannous (II) ion salts has been a problem in the art due to the above handling issues. It has been proven difficult to obtain a flow of the primary tin ion salt from a storage container. The design for an ideal flow is thought to be a simple storage container with a wall angle of a sufficiently steep gradient to facilitate the flow of the mass. However, since stannous chloride solidifies very easily, a simple design for the flow of the mass is ineffective.

[0006] Because of these problems, drying aids are used. Common desiccants are generally anhydrous inorganic salts that acquire waters of hydration when exposed to moist air or a wet solution. In the most common desiccants, such as sodium or magnesium sulfate, the crystals form larger lumps when they absorb water. In organic laboratory techniques, organic solvents are dried by using anhydrous salts. Other drying aids include CaCl2, CaO, zeolites, and silica gel.

[0007] Another way to address the problems associated with the hygroscopicity of the primary tin salts is the use of anti-caking agents, which can improve flow, reduce compaction, and thus reduce flow restrictions during processing. Anti-caking agents function by adsorbing excess moisture or by coating the particles to make them less likely to adsorb water. Other compounds, such as potassium nitrate, are known to experience similar problems to stannous chloride.

[0008] Another objective involves finding a composition that is compatible with a moisture-proof agent or drying aid for a hygroscopic fluoride salt used in dental care formulations. These moisture-proof agents need to be non-toxic, of high purity, and available in food grade or pharmaceutical grade. Furthermore, the moisture-proof agent needs to have good drying properties and / or fluidity with respect to the primary tin salts. SUMMARY OF THE INVENTION

[0009] A composition is provided that includes a particulate source of a stannous salt, alumina or a combination of aluminas, and a moisture-proof agent or desiccant. The terms moisture-proof agent and drying aid are used interchangeably throughout this application. The particulate stannous salt can be selected from stannous chloride, stannous fluoride, and / or stannous pyrophosphate. The alumina can be selected from spray-dried alumina, rotary calcined alumina, fumed alumina, pearled alumina, or combinations thereof. The desiccant can be any drying aid known in the art.

[0010] Also provided is a method for improving the fluidity of a particulate stannous salt by adding alumina and a drying aid to a particulate stannous source such as stannous chloride, stannous fluoride, and / or stannous pyrophosphate.

[0011] Further provided is a composition that can be used in oral care formulations such as toothpaste.

[0012] This summary is provided to introduce selected concepts in a simplified form that will be further detailed in the "Detailed Description" below. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.

DETAILED DESCRIPTION OF THE INVENTION

[0013] The following "Modes for Carrying Out the Invention" are essentially merely illustrative and are not intended to limit the present invention or its uses and applications. Unless specifically stated or apparent from the context, as used herein, the term "about" is understood to be within the normal tolerance in the art, for example, within two standard deviations of the average. "About" can be understood to be within 10%, 5%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Alternatively, "about" can be understood to mean the exact value stated. Unless apparent from the context, all numerical values provided herein are modified by the term "about".

[0014] In some embodiments of the present composition, the composition comprises a particulate source of stannous salt, alumina, and a drying aid. The stannous salt can be selected from stannous chloride, stannous fluoride, and stannous pyrophosphate. The stannous salt can be derived from one or more of the stannous salts or can be a single salt such as stannous chloride.

[0015] The anhydrous grade can be supplied in various forms, namely, powder form, flake form, and pellet form. Stannous chloride dihydrate is commercially available from various suppliers. Physical properties include a colorless crystalline substance with a slight characteristic odor, poor flowability, and a relatively short shelf life. However, the disadvantages of using stannous chloride in either the dihydrate form or the anhydrous form are manufacturing constraints both during transportation and handling. Both the dihydrate form and various anhydrous forms are, to a greater or lesser extent, hygroscopic, making it difficult to have flowability during processing and having poor activity over the shelf life of the material. Stannous chloride is also an aggressive reducing agent for some metals. This property can result in the formation of unwanted compounds as the substance cements and locates on dead spots within the storage container.

[0016] In some embodiments of the composition, stannous chloride can be selected from stannous chloride dihydrate, stannous chloride anhydride, and combinations thereof.

[0017] In some embodiments of the composition, the alumina can have an average particle size of about 0.4 micrometers (μm) to about 100 μm, or about 1 μm to about 90 μm, or about 2 μm to about 80 μm, or about 2 μm to about 30 μm when measured by a laser diffraction particle size analyzer using Horiba LA-960. As an example, hydrophilic fumed alumina particles, which are a crystalline material of alumina and anatase with a white, fluffy appearance, manufactured by Evonik, VP AEROPERL® Alu 100 / 30, which is a high-purity powder, or ULTRA® HPP manufactured by Alpha HPA, which is a rotary-fired high-purity gamma alumina with spherical particles, can be mentioned.

[0018] Without being bound by theory, it is believed that the fineness of the metal oxide can encapsulate the stannous salt particles. The metal oxide, i.e., alumina, acts as a spacer or carrier between individual tin particles, keeps the tin particles separated from each other, and ultimately reduces the adhesion force.

[0019] Since alumina has a positive charge, it neutralizes the negative charge of the polymer powder or negatively charged particles. This makes the powder electrically neutral and thus resistant to caking and sticking to walls, pipes, and each other.

[0020] In some embodiments of the composition, the alumina is mixed with the stannous salt in the range of about 0.5 to 10%, and about 0.5 to 5% by weight of alumina can be mixed.

[0021] In some embodiments of the composition, the ratio of particulate stannous salt to alumina may be about 9:1 to 199:1, or may be about 19:1 to 199:1.

[0022] In still other embodiments of the composition, the ratio of the drying aid to alumina can be from about 10:1 to 2:1, or from about 3:1 to 5:1.

[0023] In some embodiments of the composition, the drying aid can be selected from calcium sulfate, magnesium sulfate, zinc stearate, and combinations thereof.

[0024] In still other embodiments of the composition, the composition further comprises one or more oral care agents selected from a fluoride ion source, a dental abrasive, a flavoring agent, a humectant, a chelating agent, and combinations thereof.

[0025] In some embodiments, the technology includes a method of improving the flowability of a particulate first tin salt. The method includes adding alumina and a drying aid to a particulate source of the first tin salt.

[0026] In some embodiments of the method, a first tin salt selected from stannous chloride, stannous fluoride, and / or stannous pyrophosphate is provided. The first tin salt can be stannous chloride such as stannous chloride dihydrate, stannous chloride anhydride, and combinations thereof.

[0027] In some embodiments of the method, the alumina added to the first tin salt can be selected from spray-dried alumina, rotary calcined alumina, fumed alumina, pearlized alumina, or combinations thereof.

[0028] In some embodiments of the method, a particulate first tin salt is provided. The alumina can have an average particle size of from about 0.4 micrometers (μm) to about 100 μm, or from about 1 μm to about 90 μm, or from about 2 μm to about 80 μm, or from about 2 μm to about 30 μm.

[0029] In some embodiments of the method, the ratio of the particulate first tin salt to alumina can be from about 9:1 to 199:1, or from about 19:1 to 199:1, and the ratio of the drying aid to alumina can be from about 10:1 to 2:1, or from about 3:1 to 5:1.

[0030] In still other embodiments of the method, the drying aid added to the particulate first tin salt can be selected from calcium sulfate, magnesium sulfate, zinc stearate, and combinations thereof.

[0031] In still other embodiments of the method, one or more oral care agents, such as a fluoride ion source, a dental abrasive, a flavoring, a humectant, a chelating agent, and combinations thereof can be added to the composition.

[0032] In other embodiments, the composition can be used in oral care formulations, such as toothpaste.

Examples

[0033] The following examples were achieved by measuring water absorption using known drying aids with stannous fluoride (SnF2) and stannous chloride (SnCl2) in a humid atmosphere. In this test, water uptake of SnF2 and SnCl2 in the presence of different moisture-proof agents or drying aids was observed.

[0034] Example 1 - Water Absorption Test Samples were prepared by mixing 3.5 grams (g) of stannous chloride (SnCl2) with 0.15 g of a moisture-proof agent (Ca3(PO4)2 or CaSO4), and samples were prepared by mixing the stannous chloride and the moisture-proof agent with 0.15 g of a flow aid (fumed alumina) as shown below in Table 1. The salt mixtures were dried in an oven at a specified time, i.e., 24 hours, at a temperature of 120°C, then placed in a dryer and cooled to room temperature and immediately weighed. Then, the salt mixtures were stored at 23°C and a constant humidity of 93% for 6 days or until equilibrium was reached, and the weight gain was recorded over time. The water absorption rate is expressed as the increase in weight present. That is, the water absorption rate (%) = [(wet weight - dry weight) / dry weight] × 100. The results can be seen in Table 1 below.

[0035]

Table 1

[0036] The results show that the composition containing the flow aid can reduce the water absorption rate of stannous chloride in the first 24 hours compared to the two-component system, and can significantly reduce the water absorption rate compared to the composition when the two-component system contains only Ca3(PO4)2 as a moisture-proof agent.

[0037] Example 2 - Water Absorption Test Similar to Example 1, the water absorption rate in a constant humidity atmosphere was measured over 6 days. Stannous chloride was mixed with various drying aids and aluminum oxide as shown in Table 2 below.

[0038]

Table 2

[0039] The results show that the drying aids Zeodent® (silica), calcium sulfate, the combination of Aeroperl® Aeroxid® (aluminum oxide) and the drying aid, and Aerosil® (silica) can reduce water absorption compared to pure stannous chloride. The weight increase caused by stannous chloride was better in some cases and worse in other cases when alumina was combined with the drying aid, but when stannous fluoride was blended with alumina, the physical properties were stable and significantly improved, and the blend was maintained in a dry state.

[0040] Example 3 - Water Absorption Test The same procedure as in Examples 1 and 2 above was followed, except that stannous fluoride was used instead of stannous chloride. The drying aids listed in Table 3 were mixed with stannous fluoride, and the water absorption rate was measured by the weight increase of the sample after 6 days in a constant humidity atmosphere.

[0041]

Table 3

[0042] The results showed that the glidant Zeodent® and tricalcium phosphate were the only drying aids that did not result in a perceptible weight gain exceeding that of stannous fluoride alone. However, when stannous fluoride was blended with alumina or alumina and calcium sulfate, the composition was able to maintain its physical properties of being fine, dry, and powdery.

[0043] Example 4 - Flowability Test In the following, the test was carried out using a Copely Flowability Tester Model BEP according to the specifications detailed in European Pharmacopoeia 2.9.16-1. In this test, 100 g of stannous chloride was blended with 1.5 - 5.0% moisture protectant and 0.5% - 5.0% glidant. This formulation was compared with a sample of stannous chloride blended with 1% Zeodent® 119 having a particle size of 6 - 15 micrometers (μm). The stannous chloride was blended with the drying aid and glidant in a tumble mixer for 10 minutes. Then, 100 g of the blend was transferred to a funnel, the shutter was removed, and the flow-through time was recorded with a stopwatch. The results can be seen in Table 4.

[0044]

Table 4

[0045] The results showed that Zeodent®, Aerosil®, and Aeroxid® stimulated the flowability of SnCl2, while a blend of 2.5% Aeroxid® in combination with a drying aid improved the flowability of SnCl2.

[0046] Example 5 - Addition of Aluminum Oxide The following tests were conducted using a 100 g sample of stannous chloride as a salt mixed with CaSO4 and zinc stearate. Aeroperl® was added to the formulation and compared with a formulation without Aeroperl®. The flow time and physical properties of the formulation were determined. The results are shown in Table 5.

[0047]

Table 5

[0048] The results show that at a concentration of 5% of calcium sulfate alone, the flow characteristics are not stimulated, but Aeroperl® stimulates at a concentration of at least 5%. On the other hand, when 2.5% of the drying aid is first mixed with SnCl2 and then Aeroperl is gradually added, 2.1% of Aeroperl is already sufficient to stimulate the powder mixture to flow. When stannous chloride is first mixed with zinc stearate, which is a drying aid, the mixture already begins to flow with 1.5% of Aeroperl®.

[0049] Example 6 - Water Absorption at a Constant Humidity In this example, following the procedure of Example 1, i.e., a mixture of a drying aid and alumina (Aeroperl®) (as shown in Table 6) was mixed with stannous chloride. The salt mixture was stored at 23 °C and 93% constant humidity for 6 days, and the weight gain was recorded over time. The results are shown in Table 6.

[0050]

Table 6

[0051] The results show that when alumina is used in combination with a drying aid, the water absorption of stannous chloride is reduced. In particular, favorable results were obtained when alumina was mixed with stannous chloride alone or with a drying aid such as CaSO4 or zinc stearate.

[0052] Example 7 - Stannous Ion Stability Test The following tests were conducted to determine the stability of stannous ions in the solid particulate composition of this preparation. In this test, a stability assay of the raw materials was carried out, and stannous fluoride mixed with 10% silica (Zeodent® 119) was compared at 23 °C and 60% relative humidity and at 80 °C and 75% relative humidity. The level of soluble tin was measured by complexometric titration.

[0053] In a 250 mL beaker, 36 g of SnF2 and 4 g of each drying aid were added (see Table 7), mixed, and stored in a drying oven at 80 °C for 24 hours. Thereafter, 60 g of H2O was added and dispersed, and the dispersion was further stirred for 12 hours. After the solution had settled, the supernatant solution was removed with a syringe, transferred to a titration template using a 0.25 μm prefilter, and measured by potentiometric titration.

[0054] When stannous salts are stored at high temperatures, for example, 80 °C, it is predicted that some of the drying aids will react with tin and thereby be bound. When stannous salts, for example, SnCl2, SnF2 or Sn2P2O7 are then dissolved in water, the concentration of free tin decreases here. A part of the tin(II) salt is also oxidized in air to tin(VI). This part is not detected by titration. Finally, tin(IV) ions are pathologically ineffective and are therefore excluded for the intended applications.

[0055] Samples of SnF2 were blended with Zeodent® 119, Aerosil® 200, and tricalcium phosphate, and the free tin ions were determined as described above. The results of the tests can be found in Tables 7a and 7b.

[0056]

Table 7

[0057] The results show that when stannous salts are mixed with alumina, the free stannous ions decrease significantly, especially by tricalcium phosphate.

[0058]

Table 8

[0059] Example 8 - Soluble Stannous in Oral Care Formulations This example shows the reduced availability of soluble tin in the presence of the anti-caking composition.

[0060] In a 250 mL beaker, a solution of 36 wt% glycerin, 0.6 wt% sodium gluconate, and 10 wt% different anti-caking agents was prepared. The total weight of each sample was adjusted with water, and a mixture of sodium fluoride and stannous chloride (0.2543 wt% and 0.654 wt%, respectively) based on the total weight of the composition was added to each sample.

[0061] Each of 50 mL of the prepared mixture was placed in a 150 mL beaker and stirred at 500 rpm for 24 hours using a magnetic stirrer, and then 3 mL of the sample was taken using a disposable syringe equipped with a 0.45 μm syringe filter. These samples were analyzed for free tin by potentiometric titration or inductively coupled plasma. The results can be seen in Table 8a and Table 8b.

[0062]

Table 9

[0063]

Table 10

[0064] The results show that the free tin ion concentration decreases by about 10% with the addition of up to 5% alumina. In contrast, 10% of the anti-caking agent results in a reduction of up to 70% of the free tin ions. Calcium sulfate, a drying aid, has little or no effect on stannous ion activity. It should be noted that 100 times the excess drying aid was used in this test.

[0065] The aforementioned tests identified calcium sulfate, zinc stearate, magnesium sulfate, pyrogenic aluminum hydroxide (Aeroxid®), and pyrogenic silicon dioxide (Aerosil®) as the most effective anti-caking agents for SnCl2.

[0066] In addition, the combination of the aforementioned anti-caking agent and aluminum hydroxide (Aeroperl® A100 / 30) further improves the flow properties of the primary tin salt.

[0067] Finally, this test unexpectedly reveals that the suppression of free tin activity by calcium sulfate is lower than that of silica-based drying or moisture-proof agents. Finally, the combination of calcium sulfate and Aeroperl® not only improves the flow properties, but also reduces the compounding cost of stannous chloride blend and improves the processability in manufacturing.

[0068] In the foregoing detailed description of the subject matter of the present invention, at least one exemplary embodiment has been presented, but it should be understood that there are a vast number of variations. It should also be understood that the exemplary embodiment or exemplary embodiments are for illustration only and are not intended to limit the scope, applicability, or configuration of the subject matter of the present invention in any way. Rather, the foregoing detailed description will likely provide a convenient roadmap for those skilled in the art to implement the exemplary embodiments of the subject matter of the present invention. It is understood that various changes can be made to the functions and configurations of the elements described in the exemplary embodiments without departing from the scope of the subject matter of the present invention as set forth in the appended claims.

Claims

1. a) a source of fine particles of a first tin salt, b) alumina, c) a drying aid, and a composition comprising the same.

2. The composition according to claim 1, wherein the first tin salt is selected from stannous chloride, stannous fluoride and / or stannous pyrophosphate.

3. The composition according to claim 1 or 2, wherein the first tin salt is stannous chloride selected from stannous chloride dihydrate, stannous chloride anhydride, and combinations thereof.

4. The composition according to any one of claims 1 to 3, wherein the alumina is selected from spray-dried alumina, rotary calcined alumina, fumed alumina, pearlized alumina or combinations thereof.

5. The composition according to any one of claims 1 to 4, wherein the source of fine particles has an average particle size of from about 0.4 micrometers (μm) to about 100 μm, or from about 1 μm to about 90 μm, or from about 2 μm to about 80 μm, or from about 2 μm to about 30 μm.

6. The composition according to any one of claims 1 to 5, wherein the ratio of particulate first tin salt to alumina can be from about 9:1 to 199:1, or from about 19:1 to 199:

1.

7. The composition according to any one of claims 1 to 6, wherein the ratio of drying aid to alumina can be from about 10:1 to 2:1, or from about 3:1 to 5:

1.

8. The composition according to any one of claims 1 to 7, wherein the drying aid is selected from calcium sulfate, magnesium sulfate, zinc stearate, or combinations thereof.

9. The composition according to any one of claims 1 to 8, further comprising one or more oral care agents selected from a fluoride ion source, a dental abrasive, a flavoring agent, a humectant, a chelating agent, or combinations thereof.

10. A method for improving the fluidity of particulate first tin salt, the method comprising: adding alumina and a drying aid to a source of fine particles of a first tin salt.

11. The method according to claim 10, wherein the first tin salt is selected from stannous chloride, stannous fluoride and / or stannous pyrophosphate.

12. The method according to claim 10 or 11, wherein the first tin salt is stannous chloride selected from stannous chloride dihydrate, stannous chloride anhydride, or combinations thereof.

13. The method according to any one of claims 10 to 12, wherein the fine particle source has an average particle size of about 0.4 micrometers (μm) to about 100 μm, or about 1 μm to about 90 μm, or about 2 μm to about 80 μm, or about 2 μm to about 30 μm.

14. a) a fine particle source of a first tin salt, b) alumina, c) a drying aid, and The oral care composition, wherein the first tin salt is selected from stannous chloride, stannous fluoride and / or stannous pyrophosphate, the alumina is selected from spray-dried alumina, rotary calcined alumina, fumed alumina, pearlized alumina or combinations thereof, and the drying aid is selected from calcium sulfate, magnesium sulfate, zinc stearate and combinations thereof.

15. The composition according to claim 14, wherein the oral care preparation is a toothpaste or gel, a mouthwash, an oral spray, a bleaching agent, a medicinal candy, or chewing gum.

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