阅读说明：本技术 三氯蔗糖的制备方法、粗产品溶液及三氯蔗糖 (Preparation method of sucralose, crude product solution and sucralose ) 是由 赵金刚 夏家信 许传久 周万全 于 2020-12-30 设计创作，主要内容包括：本申请提供了三氯蔗糖的制备方法及其粗产品溶液,其制备方法包括：将三氯蔗糖-6-乙酯溶于甲醇中,形成三氯蔗糖-6-乙酯反应液；向三氯蔗糖-6-乙酯反应液中加入叔丁胺作为催化剂,在预设条件下反应,以使三氯蔗糖-6-乙酯发生脱酰基反应,形成三氯蔗糖混合溶液；对三氯蔗糖混合溶液进行蒸馏,得到三氯蔗糖粗产品溶液。本申请的有益效果在于：采用挥发性的叔丁胺作为催化剂,在高效可靠地催化三氯蔗糖-6-乙酯脱酰基化反应的同时,可通过简单的蒸馏工艺即可去除催化剂并回收利用,简化了分离催化剂的工艺步骤,减少了物料消耗和废水的产生量,极大程度上降低了三氯蔗糖的生产成本；且有利于清洁生产。(The application provides a preparation method of sucralose and a crude product solution thereof, wherein the preparation method comprises the following steps: dissolving sucralose-6-ethyl ester in methanol to form a sucralose-6-ethyl ester reaction solution; adding tert-butylamine serving as a catalyst into the sucralose-6-ethyl ester reaction liquid, and reacting under a preset condition to enable the sucralose-6-ethyl ester to generate deacylation reaction to form a sucralose mixed solution; and distilling the sucralose mixed solution to obtain a sucralose crude product solution. The beneficial effect of this application lies in: volatile tert-butylamine is used as a catalyst, the catalyst can be removed and recycled through a simple distillation process while the deacylation reaction of the sucralose-6-ethyl ester is catalyzed efficiently and reliably, the process step of separating the catalyst is simplified, the material consumption and the production amount of wastewater are reduced, and the production cost of the sucralose is reduced to a great extent; and is beneficial to clean production.)

1. A method for preparing sucralose, comprising:

a dissolving step: dissolving sucralose-6-ethyl ester in methanol to form a sucralose-6-ethyl ester reaction solution;

a catalysis step: adding tert-butylamine serving as a catalyst into the sucralose-6-ethyl ester reaction liquid, and reacting under a preset condition to enable the sucralose-6-ethyl ester to generate deacylation reaction to form a sucralose mixed solution; and

impurity removal: and distilling the sucralose mixed solution to obtain a sucralose crude product solution.

2. The method of claim 1, further comprising:

and (3) catalyst recovery: and recovering and reusing the catalyst distilled in the impurity removal step.

3. The method of claim 1, further comprising:

and a refining step, wherein the sucralose crude product solution is purified and refined to improve the purity of the sucralose.

4. The method according to claim 1, wherein the amount of methanol is 3 to 10mL per gram of sucralose-6-ethyl ester.

5. The method according to claim 1, wherein the tert-butylamine is used in an amount of 0.02 to 0.2g by mass per g of sucralose-6-ethyl ester.

6. The method according to claim 1, characterized in that in the catalytic step, the preset conditions are: under the condition of stirring, the reaction temperature is set to be 10-60 ℃, and the reaction time is set to be 0.5-24 h.

7. The method according to claim 1, wherein in the step of removing impurities, the distillation temperature is 20-60 ℃, the distillation pressure is 10-100 kPa, and the distillation time is 0.5-6 h.

8. The method of claim 1, further comprising:

a crystallization step: and crystallizing and purifying the sucralose crude product solution to obtain sucralose crystals.

9. A sucralose crude product solution prepared by the preparation method of any one of claims 1 to 7.

10. A sucralose purified by crystallization from the crude sucralose solution of claim 9.

Technical Field

The invention belongs to the technical field of fine chemical engineering, and particularly relates to a preparation method of sucralose, a crude product solution of the sucralose, and the sucralose.

Background

Sucralose belongs to a new generation sweetener, has the advantages of high sweetness, no calorie, good stability, high safety and the like, and has very wide market prospect. The process for synthesizing sucralose has been a major advance since the advent of sucralose. So far, the mainstream synthesis process is a single-group protection method: the 6-hydroxyl with the highest activity of the sucrose is selectively protected, and is usually in the form of acetate, namely sucrose-6-ethyl ester is generated, the three hydroxyls at the 4, 1 'and 6' positions of the sucrose-6-ethyl ester are subjected to selective chlorination reaction to generate sucralose-6-ethyl ester, and the sucralose-6-ethyl ester is deacetylated to generate sucralose.

For the deacetylation step, the existing process basically adopts catalytic amount of sodium methoxide (MeONa) as catalyst, and carries out alcoholysis in methanol (MeOH) to remove acetyl, generate sucralose and byproduct methyl acetate, etc. The adoption of the MeONa/MeOH catalytic system has the advantages of mild conditions, rapid reaction, high yield and the like, but also has certain disadvantages, such as complicated process steps, large solvent consumption and more waste water generated by resin regeneration; MeONa is relatively expensive and cannot be recycled, increasing production costs, etc.

Therefore, the process for synthesizing the sucralose by removing the acyl group from the sucralose-6-ethyl ester has great improvement and promotion space. It should be noted that the statements herein merely provide background information related to the present application and may not necessarily constitute prior art.

Disclosure of Invention

In view of the above, the present application has been developed to provide a method of sucralose preparation, a crude solution, and triple-filtered sucrose that overcome or at least partially solve the above problems.

According to one aspect of the present application, there is provided a method for preparing sucralose, comprising:

a dissolving step: dissolving sucralose-6-ethyl ester in methanol to form a sucralose-6-ethyl ester reaction solution;

a catalysis step: adding tert-butylamine serving as a catalyst into the sucralose-6-ethyl ester reaction liquid, and reacting under a preset condition to enable the sucralose-6-ethyl ester to generate deacylation reaction to form a sucralose mixed solution; and

impurity removal: and distilling the sucralose mixed solution to obtain a sucralose crude product solution.

According to another aspect of the present application, there is provided a crude sucralose solution prepared by the above-mentioned preparation method.

According to another aspect of the present application, there is provided a sucralose prepared by crystallization and purification of the crude sucralose solution prepared as above.

To sum up, the beneficial effect of this application lies in: volatile organic amine is used as a catalyst, the catalyst can be separated and recycled through a simple distillation process while the deacylation reaction of the sucralose-6-ethyl ester is catalyzed efficiently and reliably, the process step of separating the catalyst is simplified, the material consumption and the generation amount of wastewater are reduced, and the production cost of the sucralose is reduced to a great extent; and is beneficial to clean production.

The foregoing description is only an overview of the technical solutions of the present application, and the present application can be implemented according to the content of the description in order to make the technical means of the present application more clearly understood, and the following detailed description of the present application is given in order to make the above and other objects, features, and advantages of the present application more clearly understandable.

Drawings

Various other advantages and benefits will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the application. Also, like reference numerals are used to refer to like parts throughout the drawings. In the drawings:

fig. 1 shows a schematic flow diagram of a method of making sucralose according to one embodiment of the present application.

Detailed Description

Exemplary embodiments of the present application will be described in more detail below with reference to the accompanying drawings. While exemplary embodiments of the present application are shown in the drawings, it should be understood that the present application may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.

Although the MeONa/MeOH (MeONa/MeOH represents that both are present at the same time, specifically, MeONa is used as a catalyst, MeOH is used as a solvent) system is used as a classical combination for deacetylating carbohydrate (i.e. zemplein reaction) and has a wide application range, the MeONa/MeOH system is used as a catalyst and has many disadvantages, for example, sodium ions brought by the catalyst MeONa are often removed by using a cationic resin, the process is complicated, and the catalyst cannot be recycled; in addition, in the process, the regeneration of the resin also generates a large amount of waste water, which is not beneficial to clean production.

The application has the conception that the organic amine with strong volatility is used as the catalyst, the catalyst can be separated and recycled by a simple distillation process while the deacylation reaction of the sucralose-6-ethyl ester is catalyzed efficiently and reliably, so that the process step of separating the catalyst is simplified, the material consumption and the generation amount of wastewater are reduced, the production cost of the sucralose is reduced to a great extent, and the clean production is facilitated.

Fig. 1 shows a schematic flow diagram of a method of making sucralose according to one embodiment of the present application, comprising:

and a dissolving step S110, dissolving the sucralose-6-ethyl ester in methanol to form a sucralose-6-ethyl ester reaction solution.

First, sucralose-6-ethyl ester is dissolved in methanol, and then the sucralose-6-ethyl ester and the methanol can form a homogeneous mixture by means of stirring and the like.

Catalytic step S120: adding tert-butylamine serving as a catalyst into the sucralose-6-ethyl ester reaction liquid, and reacting under a preset condition to perform deacylation reaction on the sucralose-6-ethyl ester to form a sucralose mixed solution.

At present, the most widely used method for preparing sucralose is a single-group protection method, taking sucralose-6-acetate as an example, and the reaction process is shown as the reaction formula (1).

Reaction formula (1)

From the reaction formula (1), it can be seen that the sucrose has the highest activity as the 6-hydroxyl group, and in the single-group protection method, the sucrose is protected by using carboxylic acid such as acetic acid, specifically, taking acetic acid as an example, the sucrose and acetic acid are subjected to esterification reaction to generate sucrose-6-ethyl ester, after the selective chlorination reaction of the three hydroxyl groups at the 4, 1 'and 6' positions is completed, the deacylation reaction is performed to finally generate sucralose, and the protection of the 6-hydroxyl group prevents the hydroxyl group at the 6 position from being substituted by a chlorine atom.

The method is mainly improved aiming at the step of deacylation, and in the prior art, sodium methoxide is generally used as a catalyst, and methanol is used as a solvent to carry out deacetylation reaction. After the deacylation reaction is completed, the resulting reaction mixture is usually treated with a cationic resin to remove sodium ions, and the treatment process is shown in reaction formula (2).

Reaction type (2)

From the reaction formula (2), after the deacylation reaction is finished, adding a cationic resin into the obtained reactant mixture, wherein the cationic resin can perform cation exchange with the generated sodium alkoxide, separating out the crude sucralose solution by filtration, and regenerating the resin after the cation exchange to obtain the cationic resin for reuse. In the process, the catalyst sodium methoxide cannot be reused, so that a large amount of waste is caused, and a large amount of waste water is generated.

In view of the above situation, in the zemplian reaction system, the inventors found that MeONa can be replaced by many different types of bases, such as strong bases, weak bases, organic bases or inorganic bases, and also include bases in supported form such as basic anion resin, which can catalyze the deacetylation process very well. The method adopts volatile tert-butylamine as a catalyst, and on one hand, the method can efficiently and reliably catalyze the deacylation reaction of sucralose-6-ethyl ester; on the other hand, the tert-butylamine can be separated, recovered and reused by simple distillation, so that the consumption of materials such as catalysts, cationic resins and the like is reduced, and the generation amount of wastewater is reduced.

Through the catalysis step, the acyl on the 6-position of the sucralose-6-ethyl ester is removed to become hydroxyl, and the sucralose-6-ethyl ester is reduced into sucralose.

And an impurity removal step S130: and distilling the sucralose mixed solution to obtain a sucralose crude product solution.

Tert-butylamine is the volatile organic matter, therefore, after the reaction, distills the three sucrose mixed solution that strain that above-mentioned obtained, can get rid of the catalyst, get rid of the catalyst method in this application very simple, only need simple conventional means can, saved the process that uses cation resin to get rid of sodium ion to reduce the production of material loss and waste water, be favorable to clean production, and very big saving technology cost.

As shown in fig. 1, volatile tert-butylamine is used as a catalyst, the catalyst can be separated and recycled through a simple distillation process while the deacylation reaction of sucralose-6-ethyl ester is catalyzed efficiently and reliably, so that the process step of separating the catalyst is simplified, the material consumption and the generation amount of wastewater are reduced, and the production cost of sucralose is reduced to a great extent; and is beneficial to clean production.

In some embodiments of the present application, the method for preparing sucralose further comprises: and (3) catalyst recovery: and (4) recovering and reusing the catalyst distilled in the impurity removal step.

The tert-butylamine may be separated from the resulting reaction mixture by distillation and then condensed for recovery, after which it may still catalyze the deacylation reaction again.

In some embodiments of the present application, the method for preparing sucralose further comprises: and a refining step, wherein the crude sucralose product solution is purified and refined to improve the purity of sucralose.

To further increase the purity of the sucralose, the sucralose may be purified by one or a combination of several of the prior art techniques.

Sources of drugs

In the present application, if not specifically stated, the conventional drugs may be commercially available products, which are not described in detail herein.

The amount and source of methanol

In some embodiments of the present application, the amount of methanol is not limited, and in other embodiments, the amount of methanol is 3 to 10mL per gram of sucralose-6-ethyl ester; if the dosage of the methanol is less than 3mL by volume, the dosage of the methanol is insufficient, and the sucralose-6-ethyl ester cannot be completely dissolved; if the amount of the methanol is more than 10mL by volume, the amount of the methanol is excessive, unnecessary waste is caused, other beneficial effects cannot be brought, and the solvent removal amount of the subsequent sucralose crystallization process is increased.

The kind and amount of catalyst

In some embodiments of the present application, volatile tert-butylamine is selected as a catalyst, and the tert-butylamine can well catalyze the deacylation reaction of sucralose-6-ethyl ester, has volatility, can be removed by distillation, and is easy to recycle.

In some embodiments of the present application, the amount of tert-butylamine is 0.02 to 0.2g by mass per g of sucralose-6-ethyl ester.

On the basis of per gram of sucralose-6-ethyl ester, if the dosage of the tert-butylamine is less than 0.02g by mass, the dosage of the catalyst is too small to catalyze the complete deacylation of the sucralose-6-ethyl ester in a short time; on the basis of per gram of sucralose-6-ethyl ester, if the dosage of the tert-butylamine is more than 0.2g by mass, the dosage of the catalyst is too much, no obvious benefit is provided, the waste of materials is caused, the alkaline environment of the reaction liquid is too strong, and unnecessary side reactions can be caused.

Preset conditions

In some embodiments of the present application, in the catalyzing step, the preset conditions are not limited, and the deacylation reaction may be performed; in other embodiments, the preset conditions are: under the condition of stirring, the reaction temperature is set to be 10-60 ℃, and the reaction time is set to be 0.5-24 h. Wherein, stirring helps reactant and catalyst reaction misce bene, makes the reaction go on smoothly. If the reaction temperature is less than 10 ℃ and the reaction time is less than 0.5h, the reaction conditions are too mild, the reaction time is too short, and the deacylation reaction cannot be completely carried out; if the reaction temperature is more than 60 ℃ and the reaction time is more than 6 hours, the reaction conditions are too severe and the reaction time is too long, which may cause unnecessary side reactions.

Distillation conditions

In some embodiments of the present application, in the step of removing impurities, the distillation conditions are not limited, and in other embodiments, the distillation temperature is 20 to 60 ℃, the distillation pressure is 10 to 100kPa, and the distillation time is 0.5 to 6 hours. If the distillation temperature is less than 20 ℃, the distillation pressure is more than 100kPa, and the distillation time is less than 0.5h, the distillation degree is not enough, and the catalyst cannot be completely removed; if the distillation temperature is higher than 60 ℃, the distillation pressure is lower than 10kPa, and the distillation time is longer than 6h, the distillation is excessive, so that the waste of time and energy consumption is caused, and other beneficial effects cannot be brought.

Variety and source of sucralose-6-ethyl ester

The sucralose-6-ethyl ester can be obtained in the process of producing sucralose by adopting the existing single group protection method, and can also be a commercially available product, which is not limited in the application.

The reaction formula (3) shows the reaction process of the preparation method of sucralose according to another embodiment of the present application, and it can be seen from the reaction formula (3) that the deacylation reaction is performed with methanol as a solvent and tert-butylamine as a catalyst to prepare sucralose, and the products include ethyl formate and tert-butylamine in addition to sucralose, and the tert-butylamine is evaporated and removed and can be recycled, thereby saving the process and material consumption.

Reaction type (3)

Measurement means

The instrumentation and test conditions for high performance liquid chromatography referred to in this application are as follows:

a Japanese Shimadzu high performance liquid chromatograph, which is matched with RID-10A refractive index detection, an LC-10ADVP high-pressure pump and a CTO-10ASVP constant temperature box; a chromatographic column: agilent XDB C18 column (250 mm. times.4.6 mm, 5 μm); mobile phase: methanol-0.125% aqueous dipotassium hydrogen phosphate (4: 6); column temperature: 30 ℃; flow rate: 1.0 mL/min. Wherein, methanol (chromatographic purity), dipotassium hydrogen phosphate (analytical purity), ultrapure water and other standard substances are needed, and the content is measured by an external standard method.

In the present application, high performance liquid chromatography can be used to determine the content of sucralose-6-ethyl ester and sucralose, and is not described in detail in each example.

The calculation method of the yield comprises the following steps:

in each example and comparative example, the judgment criteria for complete conversion of sucralose-6-ethyl ester are as follows: sampling the reaction system, and measuring the high performance liquid chromatography of the sampled product, wherein the relative peak area of the sucralose-6-ethyl ester in the rest other species displayed on the chromatogram is less than or equal to 0.5 percent, except the solvent peak.

The reaction yield was: and determining the percentage of the actual yield of the sucralose to the theoretical yield of the reaction by using a high performance liquid chromatography external standard method.

Compared with the prior art, the process is simple and easy to operate, materials are saved, the crude product solution of the sucralose is obtained by any one of the methods, and the obtained crude product solution of the sucralose is crystallized and refined to obtain high-purity sucralose crystals. The crystallization refinement can be achieved by one or a combination of several methods in the prior art.

Example 1

100 g of fully dried sucralose-6-ethyl ester was added to a 1000 ml round bottom flask, and 300 ml of methanol was added and fully dissolved to form a homogeneous solution. A mechanical stirring device was attached to the flask, stirring was started, and 3 g of tert-butylamine was added dropwise from the dropping funnel. After the addition is finished, the reaction is maintained at 50 ℃ for 12 hours, the high performance liquid chromatography shows that the residual of the sucralose-6-ethyl ester is less than or equal to 0.5 percent (relative peak area), and the stirring is stopped. The reaction solution is distilled by a rotary evaporator under the conditions of the temperature of 30 ℃ and the pressure of 80kPa, about 150 ml of distillate is distilled to be a mixture of tert-butylamine and methanol, and the tert-butylamine in the reaction solution is removed at the moment, so that the sucralose product can be further purified according to the conventional method. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography is 88%.

Example 2

100 g of fully dried sucralose-6-ethyl ester was added to a 2000 ml three-neck round-bottom flask, and 1000 ml of methanol was added to fully dissolve the sucralose to form a homogeneous solution. A mechanical stirring device was attached to the flask, stirring was turned on, and 20 g of tert-butylamine were added dropwise from the dropping funnel. After the addition, the reaction was maintained at room temperature (25 ℃) for 2 hours, high performance liquid chromatography showed that the sucralose-6-ethyl ester remained at or below 0.5% (relative peak area), and the stirring was stopped. The reaction solution is distilled by a rotary evaporator under the conditions of the temperature of 50 ℃ and the pressure of 20kPa, about 400 ml of distillate is distilled to be a mixture of tert-butylamine and methanol, the tert-butylamine in the reaction solution is removed at the moment, and the sucralose product can be further purified according to the conventional method. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography is 85%.

Example 3

100 g of fully dried sucralose-6-ethyl ester was added to a 1000 ml round bottom flask, and 600 ml of methanol was added to fully dissolve the sucralose to form a homogeneous solution. A mechanical stirring device was attached to the flask, stirring was started, and 2g of tert-butylamine was added dropwise from the dropping funnel. After the addition is finished, the reaction is maintained at 40 ℃ for 24 hours, the high performance liquid chromatography shows that the residual of the sucralose-6-ethyl ester is less than or equal to 0.5 percent (relative peak area), and the stirring is stopped. The reaction solution is distilled by a rotary evaporator under the conditions of 40 ℃ of temperature and 40kPa to obtain a distillate of about 200 ml, which is a mixture of tert-butylamine and methanol, wherein the tert-butylamine in the reaction solution is removed at the moment, and the sucralose product can be further purified according to a conventional method. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography was 82%.

Example 4

100 g of fully dried sucralose-6-ethyl ester was added to a 1000 ml round bottom flask, and 400 ml of methanol was added to fully dissolve the sucralose to form a homogeneous solution. A mechanical stirring device was attached to the flask, stirring was started, and 5 g of tert-butylamine were added dropwise from the dropping funnel. After the addition, the reaction was maintained at room temperature (25 ℃) for 6 hours, high performance liquid chromatography showed that the sucralose-6-ethyl ester remained at or below 0.5% (relative peak area), and the stirring was stopped. The reaction solution is distilled by a rotary evaporator under the conditions of 50 ℃ of temperature and 50kPa to obtain a distillate of about 200 ml, which is a mixture of tert-butylamine and methanol, wherein the tert-butylamine in the reaction solution is removed at the moment, and the sucralose product can be further purified according to a conventional method. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography is 92%.

Example 5 (recovery of tert-butylamine for use)

100 g of fully dried sucralose-6-ethyl ester was added to a 1000 ml round bottom flask, and 300 ml of methanol was added and fully dissolved to form a homogeneous solution. A mechanical stirring device was attached to the flask, and stirring was turned on, and 200 ml of a mixture of tert-butylamine and methanol recovered by distillation in example 4 was added dropwise using a dropping funnel. After the addition, the reaction was maintained at room temperature (25 ℃) for 6 hours, high performance liquid chromatography showed that the sucralose-6-ethyl ester remained at or below 0.5% (relative peak area), and the stirring was stopped. The reaction solution is distilled by a rotary evaporator under the conditions of 50 ℃ of temperature and 50kPa to obtain a distillate of about 200 ml, which is a mixture of tert-butylamine and methanol, wherein the tert-butylamine in the reaction solution is removed at the moment, and the sucralose product can be further purified according to a conventional method. The yield of sucralose generated by the deacetylation reaction of sucralose-6-ethyl ester determined by high performance liquid chromatography is 89%.

Comparative example 1 (deacetylation of MeONa/MeOH System)

100 g of sucralose-6-ethyl ester and 300 ml of methanol are added into a three-neck round-bottom flask with the volume of 1000 ml, and are fully dissolved to form a homogeneous solution, and 2g of sodium methoxide is added into the solution. A mechanical stirring device is arranged on a flask, stirring is started, reaction is carried out for 6 hours at 25 ℃, then the high performance liquid chromatography is used for measuring that the residual of the sucralose-6-ethyl ester is less than or equal to 0.5 percent (relative peak area), and the stirring is stopped. Adding a proper amount of acidic cation resin into the reaction solution, and keeping stirring at a low speed until the pH of the reaction solution is 7. Filtering to remove resin, and further purifying the sucralose product according to conventional method. In the process, sodium methoxide cannot be recycled, cation resin is required to remove sodium ions, acid and alkali are required to be used for multiple leaching exchange treatment of the used acidic cation resin, and the acidic cation resin can be recycled, and a large amount of wastewater is generated in the process. The yield of sucralose was 89% as determined by high performance liquid chromatography.

It can be seen from examples 1-5 and comparative example 1 that, by using the method of the present application, tert-butylamine as a catalyst, the catalyst can be separated by distillation while efficiently and reliably catalyzing the deacylation reaction of sucralose-6-ethyl ester, and the mixture of the distilled catalyst and methanol can be directly reused, thereby saving the catalyst post-treatment process.

To sum up, the beneficial effect of this application lies in: volatile tert-butylamine is used as a catalyst, the catalyst can be removed and recycled through a simple distillation process while the deacylation reaction of the sucralose-6-ethyl ester is catalyzed efficiently and reliably, the process step of separating the catalyst is simplified, the material consumption and the generation amount of wastewater are reduced, and the production cost of the sucralose is reduced to a great extent; and is beneficial to clean production.

While the foregoing is directed to embodiments of the present application, other modifications and variations of the present application may be devised by those skilled in the art in light of the above teachings. It should be understood by those skilled in the art that the foregoing detailed description is for the purpose of better explaining the present application, and the scope of protection of the present application shall be subject to the scope of protection of the claims.

Furthermore, those skilled in the art will appreciate that while some embodiments described herein include some features included in other embodiments, rather than other features, combinations of features of different embodiments are meant to be within the scope of the application and form different embodiments. For example, in the following claims, any of the claimed embodiments may be used in any combination.