A temperature-sensitive controlled-release oral product and preparation method thereof

Abstract

The present invention discloses a temperature-sensitive controlled-release oral product and a preparation method thereof, and relates to the technical field of oral product preparation. The preparation method of the temperature-sensitive controlled-release oral product comprises the following steps: S1. preparing a temperature-sensitive pH regulator microcapsule; S2. preparing an oral product powder; S3. uniformly mixing the temperature-sensitive pH regulator microcapsule obtained in step S1 with the oral product powder obtained in step S2, so that the overall pH is between 8 and 9, and the temperature-sensitive controlled-release oral product is obtained. The present invention provides a temperature-sensitive controlled-release oral product and a preparation method thereof, wherein the temperature-sensitive pH regulator microcapsule is used to replace the traditional pH regulator, nicotine is not easily lost, the aroma is stable, it is not easy to change color, and there is no pungent nicotine smell; at the same time, ammonium chloride is added to the oral product powder, and the salty and fresh taste of ammonium chloride can be maintained for a long time; after the oral product is taken in, carbonate is released, free nicotine is precipitated, and the high is fast.

Description

Technical Field

[0001] The present invention relates to the technical field of preparation of oral products, and in particular to a temperature-sensitive controlled-release oral product and a preparation method thereof. Background Art

[0002] The traditional wet method for preparing oral products generally involves directly mixing a pH regulator with materials such as resin nicotine, flavors, and ammonium chloride, which results in the precipitation of free nicotine, the reaction of flavor acid monomers with alkali, and the consumption of ammonium chloride. These reactions will cause the prepared oral products to have a worse head feel, a weakened aroma, and a worse taste. In addition, under the storage conditions of relatively low temperatures in cold regions, the preservation of pH regulators is also a major problem. Based on this, the present invention provides a temperature-sensitive controlled-release oral product and a preparation method thereof.

[0003] For areas with lower temperatures (0-10°C), cocoa butter with a melting point close to that of the human body is used to embed the pH regulator (carbonate). Under outdoor and indoor storage conditions, the temperature is lower than the melting point of cocoa butter, and the embedding structure is stable; once it enters the human mouth, the temperature is slightly higher than the melting point of cocoa butter, and the smaller cocoa butter microcapsules can dissolve quickly in a short period of time, allowing the internal pH regulator to precipitate, releasing free nicotine. Summary of the invention

[0004] In order to solve the above technical problems, the present invention provides a temperature-sensitive controlled-release oral product and a preparation method thereof, using cocoa butter with a melting point of 34-36°C and hydrophilic colloid (hydrophilic gel) as wall materials and carbonate as core materials to produce a temperature-sensitive pH regulator microcapsule. The temperature-sensitive pH regulator microcapsule is used to replace the traditional pH regulator to achieve:

[0005] 1) Under the storage conditions of low temperature in cold regions, the thermosensitive pH regulator microcapsules do not disintegrate, the pH of the oral powder system is 6-6.5, free nicotine is not precipitated, and the acid monomers of the flavor rarely react with the base. This makes the oral product less likely to change color and the aroma is stable;

[0006] 2) Unique taste, with a special salty and fresh taste of ammonium chloride, and because ammonium chloride does not directly react with alkali, this taste can be maintained for a long time;

[0007] 3) After entering the mouth, at a temperature of about 37°C, the pH adjuster (carbonate) is released, causing the overall pH to reach between 8 and 9, free nicotine precipitates, and the high quickly sets in.

[0008] The specific technical solutions include the following:

[0009] In a first aspect, a method for preparing a temperature-sensitive controlled-release oral preparation is provided, comprising the following steps:

[0010] S1. Preparation of thermosensitive pH regulator microcapsules: placing cocoa butter in anhydrous ethanol, stirring in a water bath, and fully dissolving to obtain a cocoa butter-anhydrous ethanol solution; then adding carbonate and hydrophilic gum to the cocoa butter-anhydrous ethanol solution, stirring and fully mixing to obtain an ethanol phase; then adding a saturated sodium carbonate aqueous solution to the ethanol phase, and fully mixing to obtain a mixed system; placing the mixed system in an ice water bath to cool, and fully stirring; filtering the sample, drying in an oven, and crushing to obtain a thermosensitive pH regulator microcapsule;

[0011] S2. Preparation of oral powder: Add filler, humectant, sweetener, cooling agent, flavoring agent, antioxidant, sodium chloride to distilled water and mix well; then add nicotine resin and mix well; finally, add ammonium chloride so that the pH is between 6-6.5 to obtain oral powder;

[0012] S3. The temperature-sensitive pH regulator microcapsules prepared in step S1 are uniformly mixed with the oral preparation powder prepared in step S2 to make the overall pH between 8 and 9, and then packed into bags at 0.55 g / bag to obtain a temperature-sensitive controlled-release oral preparation.

[0013] Furthermore, in step S1, the weight portion of cocoa butter is 5-10 parts, the weight portion of anhydrous ethanol is 20-50 parts, the weight portion of carbonate is 2-10 parts, the weight portion of hydrophilic gum is 2-10 parts, and the weight portion of saturated sodium carbonate aqueous solution is 20-50 parts.

[0014] Furthermore, in step S1, the carbonate is sodium carbonate, and the hydrophilic gum is one or more of konjac gum, maltodextrin, gum arabic, soy protein isolate and whey protein, xanthan gum, gelatin, sodium alginate, acrylic resin, and ethyl cellulose.

[0015] Furthermore, in step S1, the temperature of the water bath stirring is 40-50°C; the temperature of the drying is 25-30°C, and the drying time is 24-48h.

[0016] Furthermore, in step S2, the weight portion of distilled water is 20-30 parts, the weight portion of filler is 30-50 parts, the weight portion of humectant is 5-15 parts, the weight portion of sweetener is 0.3-1.5 parts, the weight portion of cooling agent is 0.2-5 parts, the weight portion of flavoring agent is 2-10 parts, the weight portion of antioxidant is 0.2-2 parts, the weight portion of sodium chloride is 0.5-5 parts, and the weight portion of nicotine resin is 5-10 parts.

[0017] Furthermore, the filler is one or more of sodium microcrystalline cellulose, starch, maltitol, mannitol, sorbitol, and xylitol, and the humectant is one or more of glycerol or propylene glycol.

[0018] Furthermore, the sweetener is one or more of acesulfame potassium, sucralose, and neotame, and the cooling agent is one or more of WS-3 (N-ethyl-2-isopropyl-5-methylcyclohexanecarboxamide), WS-5 (N-(ethoxycarbonylmethyl)-para-alkane-3-carboxamide) and WS-23 (N,2,3-trimethyl-2-(1-methylethyl)-butyramide).

[0019] Furthermore, the flavoring agent is one or more of strawberry flavor, sweet orange flavor, watermelon flavor, lemon flavor, mint flavor, and wintergreen flavor.

[0020] Furthermore, the antioxidant is one or more of sodium sulfite, sodium thiosulfate, sodium ascorbate, and tea polyphenols.

[0021] In a second aspect, a temperature-sensitive controlled-release oral preparation is provided, which is prepared by the preparation method of the temperature-sensitive controlled-release oral preparation described in the first aspect.

[0022] The beneficial effects of the present invention are:

[0023] The present invention aims at a series of side effects caused by direct contact of pH regulator with other unstable components in the traditional wet method for preparing oral products. The temperature-sensitive cocoa butter and hydrophilic colloid (hydrophilic glue) are used as wall materials and carbonate is used as core material to produce temperature-sensitive pH regulator microcapsules. The temperature-sensitive pH regulator microcapsules are used to replace the traditional pH regulator, and ammonium chloride is added to the oral product powder. The following problems are solved:

[0024] 1) Nicotine is not easily lost, the aroma is stable, and it is not easy to change color;

[0025] 2) No pungent nicotine smell;

[0026] 3) The salty and fresh taste of ammonium chloride can be maintained for a long time;

[0027] 4) After entering the mouth, at a temperature of about 37°C, the pH adjuster (carbonate) is released, making the overall pH between 8-9, free nicotine precipitates, and the high quickly comes. DETAILED DESCRIPTION

[0028] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] It should be understood that when used in this specification and the appended claims, the terms "include" and "comprises" indicate the presence of described features, integers, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or combinations thereof.

[0030] It should also be understood that the terms used in this specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. As used in the specification of the present invention and the appended claims, unless the context clearly indicates otherwise, the singular forms "a", "an" and "the" are intended to include plural forms.

[0031] It should be further understood that the term "and / or" used in the present description and the appended claims refers to any and all possible combinations of one or more of the associated listed items, and includes these combinations.

[0032] In order to more fully understand the technical content of the present invention, the technical solution of the present invention is further introduced and illustrated in conjunction with specific embodiments below.

[0033] Example 1

[0034] A method for preparing a temperature-sensitive controlled-release oral preparation comprises the following steps:

[0035] S1. 8.0g of cocoa butter is placed in 32mL of anhydrous ethanol, stirred in a water bath at a temperature of 45°C, fully dissolved, and a 0.25g / mL cocoa butter-anhydrous ethanol solution is obtained; then 3.0g of carbonate (sodium carbonate) and 4.0g of hydrophilic glue (konjac gum) are added to the cocoa butter-anhydrous ethanol solution by weight, stirred and fully mixed to obtain an ethanol phase; then 30mL of saturated sodium carbonate aqueous solution is added to the ethanol phase, fully mixed to obtain a mixed system; the mixed system is placed in an ice water bath to cool, and fully stirred; the sample is filtered, and the temperature-sensitive pH regulator microcapsules are obtained after drying and crushing in an oven at a drying temperature of 30°C and a drying time of 24h;

[0036] S2. Add 40 g of filler (30 g of microcrystalline cellulose and 10 g of xylitol), 10 g of humectant (propylene glycol), 0.6 g of sweetener (0.5 g of acesulfame potassium and 0.1 g of sucralose), 2 g of cooling agent (WS-23), 10 g of flavoring agent (mint flavor), 3 g of antioxidant (sodium ascorbate), and 2 g of sodium chloride to 20 mL of distilled water and mix well; then add 8 g of nicotine resin and mix well; finally, add ammonium chloride so that the pH is between 6.3 to obtain an oral product powder;

[0037] S3. The temperature-sensitive pH regulator microcapsules prepared in step S1 are uniformly mixed with the oral preparation powder prepared in step S2 to make the overall pH at 8.6, and then packed at 0.55 g / bag to obtain the temperature-sensitive controlled-release oral preparation of Example 1.

[0038] Example 2

[0039] A method for preparing a temperature-sensitive controlled-release oral preparation comprises the following steps:

[0040] S1. 8.0 g of cocoa butter is placed in 32 mL of anhydrous ethanol, stirred in a water bath at a temperature of 45° C. to fully dissolve, and a 0.25 g / mL cocoa butter-anhydrous ethanol solution is obtained; then 3.0 g of carbonate (sodium carbonate) and 4.0 g of hydrophilic gum (gum arabic) are added to the cocoa butter-anhydrous ethanol solution, stirred and fully mixed to obtain an ethanol phase; then 30 mL of saturated sodium carbonate aqueous solution is added to the ethanol phase, and fully mixed to obtain a mixed system; the mixed system is placed in an ice water bath to cool down, and fully stirred; the sample is filtered, and dried in an oven at a drying temperature of 30° C. for a drying time of 24 h, and then crushed to obtain a thermosensitive pH regulator microcapsule;

[0041] S2. Add 40 g of filler (30 g of microcrystalline cellulose and 10 g of xylitol), 10 g of humectant (propylene glycol), 0.6 g of sweetener (0.5 g of acesulfame potassium and 0.1 g of sucralose), 2 g of cooling agent (WS-23), 10 g of flavoring agent (mint flavor), 3 g of antioxidant (sodium ascorbate), and 2 g of sodium chloride to 20 mL of distilled water and mix well; then add 8 g of nicotine resin and mix well; finally, add ammonium chloride so that the pH is between 6.3 to obtain an oral product powder;

[0042] S3. The temperature-sensitive pH regulator microcapsules prepared in step S1 are uniformly mixed with the oral preparation powder prepared in step S2 to make the overall pH at 8.6, and then packed at 0.55 g / bag to obtain the temperature-sensitive controlled-release oral preparation of Example 2.

[0043] Example 3

[0044] A method for preparing a temperature-sensitive controlled-release oral preparation comprises the following steps:

[0045] S1. 8.0 g of cocoa butter is placed in 32 mL of anhydrous ethanol, stirred in a water bath at a temperature of 45° C. to fully dissolve, and a 0.25 g / mL cocoa butter-anhydrous ethanol solution is obtained; then 3.0 g of carbonate (sodium carbonate) and 4.0 g of hydrophilic gel (sodium alginate) are added to the cocoa butter-anhydrous ethanol solution, stirred and fully mixed to obtain an ethanol phase; then 30 mL of saturated sodium carbonate aqueous solution is added to the ethanol phase, and fully mixed to obtain a mixed system; the mixed system is placed in an ice water bath to cool down, and fully stirred; the sample is filtered, and dried in an oven at a drying temperature of 30° C. for a drying time of 24 h, and then crushed to obtain a temperature-sensitive pH regulator microcapsule;

[0046] S2. Add 40 g of filler (30 g of microcrystalline cellulose and 10 g of xylitol), 10 g of humectant (propylene glycol), 0.6 g of sweetener (0.5 g of acesulfame potassium and 0.1 g of sucralose), 2 g of cooling agent (WS-23), 10 g of flavoring agent (mint flavor), 3 g of antioxidant (sodium ascorbate), and 2 g of sodium chloride to 20 mL of distilled water and mix well; then add 8 g of nicotine resin and mix well; finally, add ammonium chloride so that the pH is between 6.3 to obtain an oral product powder;

[0047] S3. The temperature-sensitive pH regulator microcapsules prepared in step S1 and the oral preparation powder prepared in step S2 are uniformly mixed to make the overall pH at 8.6, and then packed at 0.55 g / bag to obtain the temperature-sensitive controlled-release oral preparation of Example 3.

[0048] Example 4

[0049] A method for preparing a temperature-sensitive controlled-release oral preparation comprises the following steps:

[0050] S1. 8.0 g of cocoa butter is placed in 32 mL of anhydrous ethanol, stirred in a water bath at a temperature of 45° C. to fully dissolve, and a 0.25 g / mL cocoa butter-anhydrous ethanol solution is obtained; then 3.0 g of carbonate (sodium carbonate) and 4.0 g of hydrophilic gum (xanthan gum) are added to the cocoa butter-anhydrous ethanol solution, stirred and fully mixed to obtain an ethanol phase; then 30 mL of saturated sodium carbonate aqueous solution is added to the ethanol phase, and fully mixed to obtain a mixed system; the mixed system is placed in an ice water bath to cool, and fully stirred; the sample is filtered, and dried in an oven at a drying temperature of 30° C. for a drying time of 24 h, and then crushed to obtain a temperature-sensitive pH regulator microcapsule;

[0051] S2. Add 40 g of filler (30 g of microcrystalline cellulose and 10 g of xylitol), 10 g of humectant (propylene glycol), 0.6 g of sweetener (0.5 g of acesulfame potassium and 0.1 g of sucralose), 2 g of cooling agent (WS-23), 10 g of flavoring agent (mint flavor), 3 g of antioxidant (sodium ascorbate), and 2 g of sodium chloride to 20 mL of distilled water and mix well; then add 8 g of nicotine resin and mix well; finally, add ammonium chloride so that the pH is between 6.3 to obtain an oral product powder;

[0052] S3. The temperature-sensitive pH regulator microcapsules prepared in step S1 are uniformly mixed with the oral preparation powder prepared in step S2 to make the overall pH at 8.6, and then packed at 0.55 g / bag to obtain the temperature-sensitive controlled-release oral preparation of Example 4.

[0053] Comparative Example 1

[0054] Compared with Example 1, the difference is that no hydrophilic glue is added in step S1, and the other conditions are the same.

[0055] Comparative Example 2

[0056] Compared with Example 1, the difference is that the temperature-sensitive pH regulator microcapsules prepared in step S1 are replaced by an equal amount of sodium carbonate powder, and the other conditions are the same.

[0057] Comparative Example 3

[0058] Compared with Example 1, the difference is that ammonium chloride is not added in step S2, and the other conditions are the same.

[0059] Comparative Example 4

[0060] Compared with Example 1, the difference is that the drying temperature in step S1 is 35° C., and the other conditions are the same.

[0061] Comparative Example 5

[0062] Compared with Example 1, the difference is that in step S3, the temperature-sensitive pH regulator microcapsules prepared in step S1 and the oral preparation powder prepared in step S2 are uniformly mixed to obtain an overall pH of 7.5, and the other conditions are the same.

[0063] Comparative Example 6

[0064] Compared with Example 1, the difference is that in step S3, the overall pH is 10 after the temperature-sensitive pH regulator microcapsules prepared in step S1 and the oral preparation powder prepared in step S2 are evenly mixed, and the other conditions are the same.

[0065] Performance Testing

[0066] Nicotine retention rate (%): After the temperature-sensitive controlled-release oral preparation was stored in a constant temperature and humidity chamber at 25°C and 75% humidity for 180 days, the nicotine retention rate was measured.

[0067] Nicotine release pattern test: The steroid method is used to determine the nicotine release pattern of temperature-sensitive controlled-release oral products. After moistening the mouth, the subject holds the oral product on the upper lip for 2 minutes, 5 minutes, and 10 minutes, then spits it out to determine the residual nicotine content: 2 minutes, 5 minutes, and 10 minutes nicotine residual rate.

[0068] Sensory description: Observe whether the sample has turned yellow and has a nicotine smell after the nicotine retention rate test. When testing the nicotine release pattern, test the stimulation, speed of getting high, and comfort of the oral product.

[0069] The temperature-sensitive controlled-release oral preparations of Examples 1-4 were subjected to performance tests, and the test results are shown in Table 1:

[0070] Table 1 Performance test results of temperature-sensitive controlled-release oral preparations of Examples 1-4

[0071]

[0072] The temperature-sensitive controlled-release oral preparations of Comparative Examples 1-6 were subjected to performance tests, and the test results are shown in Table 2:

[0073] Table 2 Performance test results of temperature-sensitive controlled-release oral preparations of Comparative Examples 1-6

[0074]

[0075]

[0076] It can be seen from the test results of Tables 1-2 that the temperature-sensitive controlled-release oral products prepared in the embodiments of the present invention are stable, not easy to change color, have no nicotine smell after 6 months of storage, and get high quickly. It can be seen from the test results of Example 1 and Comparative Examples 1-6 that the molding of the temperature-sensitive pH regulator microcapsules in the present invention depends on the hydrophilic glue. When there is no hydrophilic glue, the wall material structure is not firm. During the storage process, carbonate (sodium carbonate) leaks, resulting in an increase in the pH of the resin nicotine, free nicotine precipitation, and an undesirable nicotine smell. In addition, the addition of ammonium chloride will bring a special salty and fresh taste on the one hand, and on the other hand, it will stimulate the oral cavity to secrete saliva and accelerate the speed of getting high. Since the temperature-sensitive pH regulator microcapsules are sensitive to temperature, when the drying temperature reaches the melting point of cocoa butter, the microcapsule system is destroyed, and the carbonate (sodium carbonate) contacts the resin nicotine, resulting in the precipitation of free nicotine. If the overall pH value is too low after adding the thermosensitive pH regulator microcapsules, although the resin nicotine will be more stable, it will lead to a slower head start. If the overall pH is too high, the alkaline burning sensation on the lips will become stronger.

[0077] In summary, the present invention provides a temperature-sensitive controlled-release oral preparation and a preparation method thereof, which has the following beneficial effects:

[0078] 1) Cocoa butter with a melting point of 34-36°C and hydrophilic colloid are used as wall materials, and carbonate is used as core material to produce thermosensitive pH regulator microcapsules. The thermosensitive pH regulator microcapsules are used to replace traditional pH regulators. After the pH regulator is released, the overall pH of the oral product reaches between 8 and 9.

[0079] 2) Ammonium chloride is added to the oral preparation powder. The ammonium chloride and the weakly alkaline resin nicotine act together to make the pH value of the oral preparation powder between 6 and 6.5 when the pH regulator microcapsules are not disintegrated.

[0080] The above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can easily think of various equivalent modifications or replacements within the technical scope disclosed by the present invention, and these modifications or replacements should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention shall be based on the protection scope of the claims.

Claims

1. A method for preparing a temperature-sensitive controlled-release oral product, characterized in that: The following steps are involved: S1. Put cocoa butter into anhydrous ethanol, stir in a water bath, and fully dissolve to obtain a cocoa butter-anhydrous ethanol solution; then add carbonate and hydrophilic gum to the cocoa butter-anhydrous ethanol solution, stir and fully mix to obtain an ethanol phase; then add a saturated sodium carbonate aqueous solution to the ethanol phase, and fully mix to obtain a mixed system; place the mixed system in an ice water bath to cool, and fully stir; filter the sample, dry it in an oven, and crush it to obtain a temperature-sensitive pH regulator microcapsule; S2. Add filler, humectant, sweetener, cooling agent, flavoring agent, antioxidant, sodium chloride to distilled water and mix well; then add nicotine resin and mix well; finally, add ammonium chloride so that the pH is between 6-6.5 to obtain an oral powder product; S3. The temperature-sensitive pH regulator microcapsules prepared in step S1 are uniformly mixed with the oral preparation powder prepared in step S2 to make the overall pH between 8 and 9, and then packed into bags at 0.55 g / bag to obtain a temperature-sensitive controlled-release oral preparation.

2. The method for preparing the temperature-sensitive controlled-release oral preparation according to claim 1, characterized in that: In step S1, the weight portion of cocoa butter is 5-10 parts, the weight portion of anhydrous ethanol is 20-50 parts, the weight portion of carbonate is 2-10 parts, the weight portion of hydrophilic gum is 2-10 parts, and the weight portion of saturated sodium carbonate aqueous solution is 20-50 parts.

3. The method for preparing the temperature-sensitive controlled-release oral preparation according to claim 2, characterized in that: In step S1, the carbonate is sodium carbonate, and the hydrophilic gum is one or more of konjac gum, maltodextrin, gum arabic, soy protein isolate and whey protein, xanthan gum, gelatin, sodium alginate, acrylic resin, and ethyl cellulose.

4. The method for preparing the temperature-sensitive controlled-release oral preparation according to claim 3, characterized in that: In step S1, the temperature of the water bath stirring is 40-50°C; the temperature of the drying is 25-30°C, and the drying time is 24-48h.

5. The method for preparing the temperature-sensitive controlled-release oral preparation according to claim 1, characterized in that: In step S2, the weight portion of distilled water is 20-30 parts, the weight portion of filler is 30-50 parts, the weight portion of humectant is 5-15 parts, the weight portion of sweetener is 0.3-1.5 parts, the weight portion of cooling agent is 0.2-5 parts, the weight portion of flavoring agent is 2-10 parts, the weight portion of antioxidant is 0.2-2 parts, the weight portion of sodium chloride is 0.5-5 parts, and the weight portion of nicotine resin is 5-10 parts.

6. The method for preparing the temperature-sensitive controlled-release oral preparation according to claim 5, characterized in that: The filler is one or more of sodium microcrystalline cellulose, starch, maltitol, mannitol, sorbitol, and xylitol, and the humectant is one or more of glycerol or propylene glycol.

7. The method for preparing the temperature-sensitive controlled-release oral preparation according to claim 6, characterized in that: The sweetener is one or more of acesulfame potassium, sucralose, and neotame, and the cooling agent is one or more of WS-3, WS-5, and WS-23.

8. The method for preparing the temperature-sensitive controlled-release oral preparation according to claim 7, characterized in that: The flavor corrector is one or more of strawberry flavor, sweet orange flavor, watermelon flavor, lemon flavor, mint flavor and wintergreen flavor.

9. The method for preparing the temperature-sensitive controlled-release oral preparation according to claim 8, characterized in that: The antioxidant is one or more of sodium sulfite, sodium thiosulfate, sodium ascorbate and tea polyphenols.

10. A temperature-sensitive controlled-release oral product, characterized in that: The invention is prepared by the method for preparing the temperature-sensitive controlled-release oral preparation according to any one of claims 1 to 9.

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