Mint throat lozenge tablet capable of fully retaining functional components and reducing floccule generation and preparation method of mint throat lozenge tablet

Abstract

The invention discloses a mint throat lozenge tablet capable of fully retaining functional components and reducing floccules and a preparation method of the mint throat lozenge tablet. The preparation method comprises the following steps: heating a solid dispersant to a molten state, adding menthol, stirring and melting, uniformly mixing, quickly cooling to enable the molten mixture to become a solid state when being cooled, crushing, and sieving to obtain menthol molten particles; placing the menthol molten particles in a boiling dryer, spraying an inclusion agent aqueous solution to carry out spray inclusion, and simultaneously carrying out low-temperature drying during the process to obtain menthol inclusion powder; carrying out superfine grinding on the plant extract I, mixing and stirring the ground plant extract I and the plant extract II at a high speed, and sieving to obtain mixed powder; placing the mixed powder in a boiling dryer, spraying a surface modifier aqueous solution to carry out spray inclusion, and simultaneously carrying out low-temperature drying during the process to obtain plant extract inclusion powder; mixing the menthol clathrate powder, the plant extract clathrate powder, sorbitol and magnesium stearate, and tabletting to obtain the mint throat lozenge tablet.

Description

Technical Field

[0001] The present invention relates to the technical field of food production processes. More specifically, it relates to a mint lozenge tablet that fully retains active ingredients and reduces the generation of flocs, and a preparation method thereof. Background Art

[0002] Mint lozenges are mainly aimed at throat discomfort caused by chronic inflammation. Generally, extracts of traditional Chinese medicine raw materials such as clearing heat and resolving phlegm, clearing heat and detoxifying, dispersing wind-heat, relieving sore throat and detumescence, such as peppermint, honeysuckle, monk fruit, and boat-fruited sterculia seeds, are commonly used, and are prepared through processes of mixing, granulation, and tableting.

[0003] Common mint lozenge tableting processes mostly adopt wet granulation. In the process, a large amount of water or ethanol aqueous solution needs to be sprayed as a wetting agent, and the obtained granules need to be dried by hot air for a long time. During this process, the active ingredient natural menthol in the active ingredients will volatilize due to heat, and the active ingredients such as chlorogenic acid in the honeysuckle extract and the anti-inflammatory and antioxidant active substance SOD in the monk fruit are easily destroyed by heat. Therefore, wet granulation not only has complex processes and high energy consumption, but also causes more damage to the main active ingredients in the mint lozenges, which is not conducive to ensuring the product quality. If dry granulation is adopted, since a large pressure is required to bind the powder particles together to form a thin sheet and then crush it, the equipment energy consumption is relatively high, and the equipment cost is also relatively high. In addition, the hardness of the obtained granules is relatively large, which will affect the dissolution rate and bioavailability of the active ingredients, and also lose the compressibility of the material, resulting in problems in tableting.

[0004] The process of directly tableting the material without granulation can avoid the influence of heat and humidity on the active ingredients, reduce the process steps, and has good economy. However, due to the high requirements for the fluidity and compressibility of the material powder, poor fluidity or compressibility of the powder will lead to uneven quality of the granules or difficulty in forming, and unable to tablet. And the powder properties such as compressibility and fluidity of most traditional Chinese medicine plant extracts cannot meet the requirements of direct tableting. Especially in mint lozenges with a relatively large proportion of plant extraction components, the direct tableting process cannot be realized. Therefore, the industry currently basically adopts wet granulation tableting, and a large amount of peppermint and other active ingredients are lost. In addition, when the menthol in the lozenge encounters repeated temperature rises and then drops during storage, it will volatilize in large amounts and then form fine crystals, which will aggregate to form flocs, affecting the product quality. These are the main technical problems that need to be solved urgently for mint lozenges. Summary of the Invention

[0005] In the existing wet granulation and tableting technology, there are common problems in menthol lozenges, such as relatively large loss of active ingredients during the preparation process, and menthol in lozenge tablets containing more menthol is likely to volatilize and crystallize due to temperature changes during storage, resulting in menthol flocs in the product packaging. An object of the present invention is to provide a preparation method of menthol lozenge tablets that can fully retain active ingredients and reduce the generation of flocs. In the present invention, the inclusion powder of menthol and the inclusion powder of plant extract are obtained by using spray inclusion technology, low-temperature drying technology, and powder surface modification technology respectively, and then the menthol lozenge tablets are prepared by tableting. Under such process steps, the loss of active ingredients such as menthol in the product is significantly reduced, and flocs are not easily generated during storage, which has a certain demonstration significance for the process improvement and quality improvement of menthol lozenge products.

[0006] Another object of the present invention is to provide a menthol lozenge tablet.

[0007] To achieve the above first object, the present invention adopts the following technical solutions:

[0008] The present invention provides a preparation method of menthol lozenge tablets that can fully retain active ingredients and reduce the generation of flocs, including the following steps:

[0009] Heat the solid dispersant to the molten state, add menthol and stir to melt, and quickly cool the molten mixture after mixing evenly to make it become solid when cooled, then crush and screen to obtain menthol molten particles;

[0010] Place the menthol molten particles in a fluidized bed dryer, spray the inclusion agent aqueous solution for spray inclusion, and at the same time perform low-temperature drying during this period to obtain menthol inclusion powder;

[0011] Ultra-finely crush the plant extract I, and after crushing, mix and stir it with the plant extract II at high speed so that the powder particles of the plant extract I are fully embedded and / or adsorbed and wrapped on the surface of the powder particles of the plant extract II, and then screen to obtain a mixed powder;

[0012] Place the mixed powder in a fluidized bed dryer, spray the surface modifier aqueous solution with a pH of 4-6 for spray inclusion, and at the same time perform low-temperature drying during this period to obtain the plant extract inclusion powder;

[0013] Mix the menthol inclusion powder, the plant extract inclusion powder, sorbitol and magnesium stearate, and tablet to obtain menthol lozenge tablets;

[0014] Among them, the plant extract I and the plant extract II contain different extract components.

[0015] In the present invention, it is intended to prepare a menthol lozenge tablet with a menthol content of 0.5% or more, added with raw materials such as honeysuckle extract and momordica grosvenori extract containing heat-sensitive components such as chlorogenic acid and SOD, and the total content of plant extracts is 10% or more. According to the traditional tableting process, such tablets not only have the problem of relatively large loss of effective components such as menthol, chlorogenic acid, and SOD, but also have the adverse situation that menthol flocs are likely to be generated during storage due to temperature changes.

[0016] To solve this problem, in the present method, on the one hand, after the plant extract I is ultrafinely pulverized, it is used as a coating particle and then mixed with the non-ultrafinely pulverized large-particle plant extract II powder by a high-speed mixing blender. During the mixing process, with the continuous action of mechanical force and intermolecular force, the coating particles are embedded and / or adsorbed and wrapped on the surface of the large-particle plant extract II powder. The mixed powder is further adsorbed, complexed, and dried at low temperature by a surface modifier to solidify the coating particles, thereby improving the fluidity and compressibility of the plant extract powder; on the other hand, a solid dispersant close to the melting temperature of menthol is selected for melting mixing first, and then sprayed into a complexing agent for complexing by low-temperature fluidized drying, reducing the volatilization of menthol. After the above treatment, the menthol complex powder and the plant extract complex powder are mixed with sorbitol and magnesium stearate, and then tableted to prepare the menthol lozenge tablet. In this preparation method, since there is no high-temperature heating link, the loss of volatile and heat-sensitive effective components such as menthol, chlorogenic acid, and SOD is reduced. In addition, with the help of the complexing technology, the situation of forming flocs due to the volatilization and crystallization of menthol during the storage of the menthol lozenge is also reduced.

[0017] Furthermore, the plant extract I includes, but is not limited to, one or more of licorice extract, sterculia lychnophora extract, and canarium album extract; the plant extract II includes, but is not limited to, honeysuckle extract and / or momordica grosvenori extract. In a specific embodiment, the plant extract I is a mixture prepared by mixing licorice extract, sterculia lychnophora extract, and canarium album extract in an equal mass ratio; the plant extract II is a mixture prepared by mixing honeysuckle extract and momordica grosvenori extract in an equal mass ratio.

[0018] It should be noted here that since more attention is paid to the loss of effective components represented by menthol, chlorogenic acid, and SOD in the present invention, the honeysuckle extract and momordica grosvenori extract containing chlorogenic acid and SOD components are selected as the plant extract II, and are fully embedded and / or adsorbed and wrapped on its surface by the plant extract I powder particles to play a protective role. Those skilled in the art can understand that if the plant extract I becomes the effective component of concern, the plant extract II can be selected to embed and / or adsorb and wrap it.

[0019] As described above, the melting temperature of the solid dispersant needs to be close to that of menthol in order to rapidly melt at a relatively low temperature and reduce the loss of menthol. As an example, the melting temperature of the solid dispersant is 45-70 °C. In a specific embodiment, the solid dispersant includes, but is not limited to, one or more of polyethylene glycol 4000, polyethylene glycol 6000, and stearic acid; preferably, the solid dispersant is selected from polyethylene glycol 4000, which has a relatively low melting temperature and is close to that of menthol, can rapidly melt, reduce the loss of menthol, and has a relatively low viscosity and good fluidity, which is beneficial to uniform dispersion and increases the protection of menthol.

[0020] The complexing agent in the aqueous solution of the complexing agent includes, but is not limited to, one or more of hydroxypropyl methylcellulose, chitosan, and sodium alginate. In a specific embodiment, the complexing agent is selected from hydroxypropyl methylcellulose, which has better water solubility and higher viscosity, requires less solvent, is beneficial to shortening the low-temperature spray drying time, and reducing the attenuation of menthol components.

[0021] The surface modifier is electrically neutral or has a charge opposite to that of the plant extract II. For example, chitosan, dextran, inulin, etc. In order to better adsorb the surface modifier on the surface of the plant extract II, it is advisable to select a surface modifier with a charge opposite to that of the plant extract II. In a specific embodiment, the surface modifier is selected from chitosan, which has a positive charge and is opposite to the charge of the above-mentioned plant extract II powder, is easy to adsorb with it, and chitosan has a certain viscosity and also plays a complexing role at the same time.

[0022] Furthermore, the concentration of the aqueous solution of the surface modifier is 14-18%. As an example, acidity regulators such as citric acid, acetic acid, and malic acid can be used to adjust the pH value of the aqueous solution of the surface modifier to the required value.

[0023] Furthermore, the spray complexing conditions are as follows: the fan frequency is 30-45 Hz, the spray gun pressure is 0.25-0.4 MPa, the flow rate is 50-100 ml / second, and the temperature of low-temperature drying is 30-40 °C. The above spray complexing conditions are applicable to the preparation of menthol complex powder and also applicable to the preparation of plant extract complex powder. In this spray complexing process, the aqueous solution of the complexing agent (or the aqueous solution of the surface modifier) is sprayed into the sample in the fluidized bed dryer by a spray pipe, while a low-temperature drying process is carried out until the moisture content ≤ 5%.

[0024] Furthermore, the particle size of the plant extract I after ultrafine grinding is controlled below 50 μm.

[0025] Furthermore, the particle size of the menthol molten particles is 70 - 90 mesh, preferably 80 mesh (about 180 μm), and the particle size of the mixed powder is 50 - 70 mesh, preferably 60 mesh (about 250 μm).

[0026] Furthermore, the concentration of the complexing agent aqueous solution is 14 - 18%.

[0027] Furthermore, by weight parts, the menthol lozenge tablets are prepared according to the following formula amounts:

[0028] Menthol 0.3 - 1.5 parts, solid dispersant 2 - 6 parts, complexing agent 0.15 - 0.30 parts, sorbitol 76 - 96 parts, magnesium stearate 1 - 2 parts, plant extract I 1 - 5 parts, plant extract II 2 - 10 parts, surface modifier 0.5 - 0.9 parts, and acidity regulator 0.02 - 0.06 parts.

[0029] Furthermore, during the preparation process, the content changes of each active ingredient are as follows: the retention rate of menthol is above 85%, the production loss rate of chlorogenic acid is below 30%, and the production loss rate of SOD activity is below 20%.

[0030] To achieve the above - mentioned second object, the present invention adopts the following technical solution:

[0031] The present invention provides a menthol lozenge tablet prepared by using the preparation method as described above.

[0032] The beneficial effects of the present invention are as follows:

[0033] The present invention provides a menthol lozenge tablet and its preparation method that can fully retain the content of active ingredients of the menthol lozenge and reduce the generation of floccules. Aiming at the common problems in the existing wet granulation and tableting technology, such as the relatively large loss of active ingredients in the preparation of menthol lozenges and the easy volatilization and crystallization of menthol in menthol lozenge tablets containing more menthol during storage, resulting in the generation of menthol floccules in the product packaging, a new process preparation method has been developed.

[0034] In this preparation method, on the one hand, the plant extract I is ultrafinely pulverized and used as the coating particles, and then mixed with the powder of other large-particle plant extract II through a high-speed mixing blender. Through the continuous action of mechanical force, intermolecular force, and van der Waals force, the coating particles are embedded, adsorbed, and wrapped on the surface of the plant extract II powder. The obtained mixed powder is further adsorbed, complexed, and dried at low temperature by a surface modifier to solidify the coating particles, improving the fluidity and compressibility of the plant extract powder. On the other hand, the solid dispersant is heated and melted, menthol is added and melted and evenly dispersed, then quickly cooled and pulverized, and the powder is sprayed into the complexing agent by low-temperature fluidized drying for complexing, reducing the volatilization of menthol. Then, the complexed plant extract powder, menthol powder, sorbitol, and magnesium stearate are mixed and directly compressed to obtain the mint lozenge compressed candy.

[0035] This process method does not go through a heating process, reducing the loss of volatile and heat-sensitive active ingredients such as menthol, chlorogenic acid, and SOD. It also reduces the formation of flocs due to the volatilization and crystallization of menthol during the storage of lozenges, which is beneficial to improving the quality and application promotion of mint lozenge products. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The following further elaborates on the specific embodiments of the present invention in conjunction with the drawings.

[0037] Figure 1 Shows a physical photograph of the sample of Example 1 of the present invention after alternating between 35°C high temperature for 5 days and 5°C low temperature for 5 days.

[0038] Figure 2 Shows a physical photograph of the tablet after pressing in Example 2 of the present invention.

[0039] Figure 3 Shows a physical photograph of the sample of Example 3 of the present invention after alternating between 35°C high temperature for 5 days and 5°C low temperature for 5 days.

[0040] Figure 4 Shows a physical photograph of the sample of Example 4 of the present invention after alternating between 35°C high temperature for 5 days and 5°C low temperature for 5 days.

[0041] Figure 5 Shows a physical photograph of the sample of Example 5 of the present invention after alternating between 35°C high temperature for 5 days and 5°C low temperature for 5 days.

[0042] Figure 6 Shows a physical photograph of the sample of Example 1 of the present invention after alternating between 35°C high temperature for 5 days and 5°C low temperature for 5 days.

[0043] Figure 7 Shows a physical photograph of the sample of Example 2 of the present invention after alternating between 35°C high temperature for 5 days and 5°C low temperature for 5 days. Detailed implementation manners

[0044] To describe the present invention more clearly, the present invention will be further described below in conjunction with preferred embodiments and the accompanying drawings. Similar components in the drawings are denoted by the same reference numerals. Those skilled in the art should understand that the content specifically described below is illustrative rather than restrictive, and should not be used to limit the protection scope of the present invention.

[0045] In the case where the purpose of the present invention is clarified and explained through the following embodiments, the components of the composition are explained with weight parts as the general standard. Without special instructions, for the sake of simplicity, the "parts" mentioned in the following content have the same meaning as weight parts.

[0046] In the present invention, samples are prepared using the raw materials and ratios shown in Table 1 and Table 2. Examples 1-5 are the adjustment processes of the formulation and preparation process of the mint lozenge tablets during the experimental stage, and the feeding amount is about 60 kg. The specific formula and preparation process are as follows:

[0047] Table 1 Various raw materials used in mint lozenge tablets

[0048]

[0049] Table 2 Raw material ratio of mint lozenge tablets in each example

[0050]

[0051] Example 1

[0052] This example provides a preparation method of mint lozenge tablets. The method adopts the traditional wet granulation method, and the specific steps are as follows:

[0053] By mass fraction, the raw materials are as follows:

[0054] Menthol 0.5%, sorbitol 83.5%, magnesium stearate 1%, plant extract I 5%, plant extract II 10%.

[0055] Crush menthol and pass through a 60-mesh sieve. Pass plant extract I, plant extract II, and sorbitol through a 60-mesh sieve, and place them in a three-dimensional motion mixer for mixing for 30 min at 8 revolutions per minute;

[0056] Place the mixed mixture in a boiling drying granulator and mix at high speed at room temperature for 10 min. Among them, set the material temperature at 55°C - 65°C. During the spraying process, the hot air inlet temperature should not exceed 70°C, the fan frequency is 30 - 45 Hz, and set the spray gun pressure at 0.25 Mpa - 0.4 Mpa.

[0057] After the spraying is completed, set the material temperature to 60 °C to fully dry the granules until the granule moisture content is ≤ 5%, and screen the granules through a 18-mesh sieve of the lifting and turning granulator. The granules are then mixed with magnesium stearate in a three-dimensional motion mixer for 15 minutes at 8 revolutions per minute. The mixed granules are pressed into tablets by a rotary high-speed tablet press, with a tablet weight of 1 g / tablet. See Tables 3 to 6 for the data of the obtained tablets, the content of active ingredients, and the formation of flocculants.

[0058] Example 2

[0059] This example provides a method for preparing mint lozenge tablets, which uses the direct mixing and pressing method. The specific steps are as follows:

[0060] By mass fraction, the raw materials are as follows:

[0061] Menthol 0.5%, sorbitol 83.5%, magnesium stearate 1%, plant extract I 5%, plant extract II 10%.

[0062] The preparation method is as follows:

[0063] Crush menthol and screen it through a 60-mesh sieve. Screen plant extract I, plant extract II, sorbitol, and magnesium stearate through a 60-mesh sieve, place them in a three-dimensional motion mixer and mix for 30 min at 8 revolutions per minute; the mixed granules are pressed into tablets by a rotary high-speed tablet press, with a tablet weight of 1 g / tablet. See Table 3 for the data of the obtained tablets. Since normal tableting cannot be carried out in this example, there is no relevant data on the content of active ingredients and the formation of flocculants.

[0064] Example 3

[0065] This example provides a method for preparing mint lozenge tablets, which uses direct mixing and pressing. The specific steps are as follows:

[0066] By mass fraction, the raw materials are as follows:

[0067] Menthol 0.5%, sorbitol 95.5%, magnesium stearate 1%, plant extract I 1%, plant extract II 2%.

[0068] The preparation method is the same as that of Example 2:

[0069] Crush menthol and screen it through a 60-mesh sieve. Screen plant extract I, plant extract II, sorbitol, and magnesium stearate through a 60-mesh sieve, place them in a three-dimensional motion mixer and mix for 30 min at 8 revolutions per minute; the mixed granules are pressed into tablets by a rotary high-speed tablet press, with a tablet weight of 1 g / tablet. After reducing the dosage of plant extract I and plant extract II, normal tableting can be carried out. See Tables 3 to 6 for the data of the obtained tablets, the content of active ingredients, and the formation of flocculants.

[0070] Example 4

[0071] This example provides a method for preparing a mint lozenge tablet, and the specific steps are as follows:

[0072] By mass fraction, the raw materials are as follows:

[0073] Menthol 0.5%, polyethylene glycol 4000 2.5%, sorbitol 93%, magnesium stearate 1%, plant extract I 1%, plant extract II 2%.

[0074] The preparation method is as follows:

[0075] Place polyethylene glycol 4000 in a water bath heating tank and heat it to melting. Then add menthol and melt and stir to disperse evenly, and quickly cool it in an ice bath to convert it into a solid state. Crush the melt and pass it through a 60-mesh sieve.

[0076] Ultra-finely crush plant extract I with a high-speed air flow crushing and classification machine, and control the particle size below 50 μm. Then place it in a high-speed stirring mixer with plant extract II and mix for 20 minutes to form composite particles, and pass through a 60-mesh sieve.

[0077] Pass sorbitol and magnesium stearate through a 60-mesh sieve, place them in a three-dimensional mixer with the menthol melt particles and the plant extract composite particles and mix for 15 minutes at a rotation speed of 8 - 12 revolutions per minute. The mixed particles are pressed into tablets by a rotary tablet press, with a tablet weight of 1 g / tablet. For the data of the obtained tablets, the content of active ingredients, and the formation of flocs, refer to Tables 3 to 6.

[0078] Example 5

[0079] This example provides a method for preparing a mint lozenge tablet, and the specific steps are as follows:

[0080] By mass fraction, the raw materials are as follows:

[0081] Menthol 0.5%, polyethylene glycol 4000 2.5%, hydroxypropyl methylcellulose 0.18%, sorbitol 92.08%, magnesium stearate 1%, plant extract I 1%, plant extract II 2%, chitosan 0.7%, citric acid 0.04%.

[0082] The preparation method is as follows:

[0083] Place polyethylene glycol 4000 in a water bath heating tank and heat it to melting. Then add menthol and melt and stir to disperse evenly, and quickly cool it in an ice bath to convert it into a solid state. Crush the melt and pass it through an 80-mesh sieve.

[0084] Prepare an aqueous solution of hydroxypropyl methylcellulose with a concentration of 16%. Place the crushed molten particles in a fluidized bed dryer. Set the fan frequency to 30 - 45 Hz, the spray gun pressure to 0.25 - 0.4 Mpa, control the flow rate at 50 - 100 ml / second, and slowly spray in the aqueous solution of hydroxypropyl methylcellulose so that the complexing agent is evenly complexed on the surface of the molten particles. During the spraying process, start low-temperature drying at 30 - 40°C until the particle moisture content ≤ 5%. Screen the particles through a 60-mesh sieve to obtain menthol complex powder.

[0085] Ultra-finely crush the plant extract I with a high-speed air flow crushing and classification machine, controlling the particle size below 50 μm. Then place it and the plant extract II in a high-speed stirring mixer and mix for 20 minutes to form composite particles, and screen through a 60-mesh sieve.

[0086] Prepare an aqueous solution of chitosan with a concentration of 16% and a pH of 4 - 6 by mixing chitosan and citric acid.

[0087] Place the composite particles of plant extracts in a fluidized bed dryer. Set the fan frequency to 30 - 45 Hz, the spray gun pressure to 0.25 - 0.4 MP, and the flow rate to 50 - 100 ml / second. Slowly spray in the aqueous solution of chitosan so that chitosan is adsorbed and complexed on the surface of the composite particles. During the spraying process, start low-temperature drying at 30 - 40°C until the particle moisture content ≤ 5%. Screen through a 60-mesh sieve to obtain the complex powder of plant extracts.

[0088] Place the two kinds of complex powders, sorbitol, and magnesium stearate in a three-dimensional mixer and mix for 15 minutes at a rotation speed of 8 - 12 revolutions per minute. Press the mixed particles with a rotary tablet press, with a tablet weight of 1 g / tablet. Refer to Tables 3 to 6 for the tablet data, the content of active ingredients, and the formation of flocculants of the obtained tablets.

[0089] Table 3 Tableting data

[0090]

[0091] Table 4 Changes in menthol content of each sample after accelerated stability test

[0092]

[0093] Table 5 Changes in chlorogenic acid content and SOD activity of each sample

[0094]

[0095] Table 6 Flocculant situation of each sample after 5 days at 35°C high temperature and then 5 days at 5°C low temperature with alternating changes

[0096]

[0097] Figures 1 - 5 The actual pictures of the samples prepared in each example are shown. The analysis is as follows in combination with Tables 3 to 6:

[0098] Example 1 adopts the traditional wet granulation method. Examples 2-5 adopt direct tableting or modify the surface of the raw material powder to improve the fluidity before tableting.

[0099] Example 1 and Example 2 use the same formula, both of which add a higher content of plant extracts. Example 1 can be pressed into tablets normally, but the loss of menthol, chlorogenic acid, and SOD components during the production process is the largest compared to other examples. No floccules were observed in Example 1 because of the high loss of menthol.

[0100] The powder of Example 2 has poor fluidity and hygroscopicity and cannot meet the tableting requirements. It is easy to stick to the punch and cannot be tableted.

[0101] In Example 3-5, the amount of plant extract added was reduced to 3%, and different process formulas were used for tableting. The loss of menthol, chlorogenic acid, and SOD components during the production process was significantly reduced compared to Example 1.

[0102] Example 3 uses direct mixing and tableting. Under the premise of adding a lower 3% plant extract, the fluidity is average and can be tableted normally, but flocs are observed in the finished product.

[0103] Example 4 uses solid dispersant polyethylene glycol 4000, and menthol is first made into solid dispersed particles by melting method, and menthol is dispersed in the pore structure formed by polyethylene glycol in a molecular state, which increases the dispersibility of menthol, and at the same time plays a certain protective role on menthol, reducing volatilization. In addition, plant extract I is ultrafinely ground as coated particles, and plant extract II is used as core particles. In a high-speed stirring mixer, the coated particles are embedded and adsorbed and wrapped on the surface of larger core particles through the continuous action of mechanical force and intermolecular force to form composite particles, which improves the fluidity and compressibility of plant extract powder. However, due to the insufficient binding force of the coated particles, they cannot be completely coated or fall off, and there are more fine powders on the surface of the tablets, which affects the sense organs. The finished product is also observed to have floccules.

[0104] Example 5 Based on Example 4, the inclusion agent hydroxypropyl methylcellulose was used to coat and low-temperature dry the menthol molten particles, further protecting the menthol and reducing its volatilization; the surface modifier chitosan was used to adsorb, encapsulate and low-temperature dry the plant extract composite particles, solidify the coated particles, further improve the fluidity of the raw materials, and solve the problem of fine powder on the tablets, and obtain good tablets. In addition, due to the further inclusion protection of menthol, no flocs were observed in the finished product after alternating high and low temperatures.

[0105] Example 1

[0106] This embodiment is a repeated experiment of Example 5 enlarged to 200 kg of feed amount.

[0107] By mass fraction, the raw materials are as follows:

[0108] Menthol 0.5%, polyethylene glycol 4000 2.5%, hydroxypropyl methylcellulose 0.18%, sorbitol 92.08%, magnesium stearate 1%, plant extract I 1%, plant extract II 2%, chitosan 0.7%, citric acid 0.04%.

[0109] The preparation method is as follows:

[0110] Place polyethylene glycol 4000 in a water bath heating tank and heat it to melting. Then add menthol and melt and stir to disperse evenly, and quickly cool it in an ice bath to convert it into a solid state. Crush the melt and pass it through an 80-mesh sieve.

[0111] Prepare an aqueous solution of hydroxypropyl methylcellulose with a concentration of 16%. Place the crushed molten particles in a fluidized bed dryer, with the fan frequency of 30 - 45 Hz, the spray gun pressure of 0.25 - 0.4 Mpa, control the flow rate at 50 - 100 ml / second, and slowly spray and add the aqueous solution of hydroxypropyl methylcellulose to evenly coat the binder on the surface of the molten particles. During the spraying process, start low-temperature drying at 30 - 40 °C until the moisture content ≤ 5%, and screen and size the particles through a 60-mesh sieve to obtain menthol inclusion powder.

[0112] Ultra-finely crush plant extract I with a high-speed air flow crushing and classification machine, and control the particle size below 50 μm. Then place it and plant extract II in a high-speed stirring mixer and mix for 20 minutes to form composite particles, and pass them through a 60-mesh sieve.

[0113] Prepare an aqueous solution of chitosan with a concentration of 16% and a pH of 4 - 6 by mixing chitosan and citric acid.

[0114] Place the plant extract composite particles in a fluidized bed dryer, with the fan frequency of 30 - 45 Hz, the spray gun pressure of 0.25 - 0.4 MP, and the flow rate of 50 - 100 ml / second. Slowly spray and add the aqueous solution of chitosan to adsorb and coat the chitosan on the surface of the composite particles. During the spraying process, start low-temperature drying at 30 - 40 °C until the moisture content ≤ 5%, and screen through a 60-mesh sieve to obtain plant extract inclusion powder.

[0115] Place the two kinds of inclusion powders, sorbitol, and magnesium stearate in a three-dimensional mixer and mix for 15 minutes at a rotation speed of 8 - 12 revolutions per minute. Press the mixed particles with a rotary tablet press, with the tablet weight of 1 g / tablet. For the data of the obtained tablets, the content of active ingredients, and the formation of flocculants, refer to Tables 7 to 10.

[0116] Example 2

[0117] This example is a technical solution in which, on the basis of Example 1, the addition amount of menthol is increased from 0.5% to 1%, and the total amount of plant extracts is increased from 3% to 15%.

[0118] By mass fraction, the raw materials are as follows:

[0119] Menthol 1%, polyethylene glycol 4000 5%, hydroxypropyl methylcellulose 0.252%, sorbitol 76.794%, magnesium stearate 1%, plant extract I 5%, plant extract II 10%, chitosan 0.9%, citric acid 0.054%.

[0120] The preparation method is the same as that of Example 1. See Tables 7 to 10 for the tablet data, the content of active ingredients, and the formation of floccules.

[0121] Table 7 Tableting data

[0122]

[0123]

[0124] Table 8 Change in menthol content of the sample in Example after accelerated stability test.

[0125]

[0126] Table 9 Changes in chlorogenic acid content and SOD activity in Example

[0127]

[0128] Table 10 Observe the floccules of the finished products in each example after alternating changes of 5 days at 35°C and 5 days at 5°C

[0129]

[0130] Example 1 is a scaled-up replication experiment of Example 5, and it is found that its reproducibility is good.

[0131] On the basis of Example 1, in Example 2, the addition amount of menthol is increased from 0.5% to 1%, and the total amount of plant extracts is increased from 3% to 15%. The tableting performance is still good, there is no fine powder of extract on the tablet surface, the losses of active ingredients such as menthol, chlorogenic acid, and SOD during the production process are low, and no floccules are observed in the finished product, verifying that the present invention can prepare menthol lozenges with a high content of active ingredients and reduce the generation of floccules.

[0132] Obviously, the above-mentioned embodiments of the present invention are merely examples for clearly explaining the present invention, rather than limitations on the implementation manners of the present invention. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the implementation manners here. Any obvious changes or modifications derived from the technical solutions of the present invention still fall within the protection scope of the present invention.

Claims

1. A method for preparing a mint throat lozenge tablet that fully retains the effective ingredients and reduces the generation of floccules, characterized in that: The following steps are involved: The solid dispersant is heated to a molten state, menthol is added and stirred to melt, and after being evenly mixed, the temperature is rapidly lowered to allow the molten mixture to become solid upon cooling, and the mixture is crushed and sieved to obtain menthol molten particles; The menthol molten particles are placed in a boiling dryer, and the inclusion agent aqueous solution is sprayed into the granulating agent for spray inclusion, and low-temperature drying is performed at the same time to obtain menthol inclusion powder; The plant extract I is ultrafinely ground, and after the grinding, it is mixed and stirred at a high speed with the plant extract II so that the powder particles of the plant extract I are fully embedded and / or adsorbed and wrapped on the surface of the powder particles of the plant extract II, and sieved to obtain a mixed powder; The mixed powder is placed in a boiling dryer, and a surface modifier aqueous solution with a pH of 4-6 is sprayed into the mixture for spray inclusion, and low-temperature drying is performed simultaneously during the process to obtain a plant extract inclusion powder; Mixing menthol inclusion powder, plant extract inclusion powder, sorbitol and magnesium stearate, and tableting to obtain mint throat lozenge tablets; Wherein, the plant extract I and the plant extract II contain different extract components.

2. The preparation method according to claim 1, characterized in that: The plant extract I is selected from one or more of liquorice extract, Sterculia lychnophora extract, and Citrus aurantium extract; The plant extract II is selected from honeysuckle extract and / or monk fruit extract.

3. The preparation method according to claim 2, characterized in that: The melting temperature of the solid dispersant is 45-70°C; The inclusion agent in the inclusion agent aqueous solution is selected from one or more of hydroxypropyl methylcellulose, chitosan, and sodium alginate; The surface modifier is electrically neutral or has a charge different from that of the plant extract II; Using an acidity regulator to adjust the pH value of the surface modifier aqueous solution, wherein the acidity regulator is selected from one or more of citric acid, acetic acid, and malic acid; Preferably, the solid dispersant is selected from one or more of polyethylene glycol 4000, polyethylene glycol 6000, and stearic acid; Preferably, the surface modifier is selected from one or more of chitosan, dextran and inulin.

4. The preparation method according to claim 1, characterized in that: The spray inclusion conditions are: fan frequency 30-45 Hz, spray gun pressure 0.25-0.4 MPa, flow rate 50-100 ml / sec, and low-temperature drying temperature 30-40°C.

5. The preparation method according to claim 1, characterized in that: The particle size of the menthol molten granules is 70-90 meshes, and the particle size of the mixed powder is 50-70 meshes.

6. The preparation method according to claim 1, characterized in that: The concentration of the inclusion agent aqueous solution is 14-18%; The concentration of the surface modifier aqueous solution is 14-18%.

7. The preparation method according to claim 1, characterized in that: The mint lozenge tablets are prepared according to the following formula in parts by weight: 0.3-1.5 parts of menthol, 2-6 parts of solid dispersant, 0.15-0.30 parts of inclusion agent, 76-96 parts of sorbitol, 1-2 parts of magnesium stearate, 1-5 parts of plant extract I, 2-10 parts of plant extract II, 0.5-0.9 parts of surface modifier and 0.02-0.06 parts of acidity regulator.

8. The preparation method according to claim 1, characterized in that: The plant extract I is a mixture of liquorice extract, Sterculia lychnophora extract, and Citrus aurantium extract in equal weight ratios; The plant extract II is a mixture of honeysuckle extract and monk fruit extract in equal weight ratio.

9. The preparation method according to claim 2, characterized in that: The content changes of each effective component during the preparation process are as follows: the menthol retention rate is above 85%, the production loss rate of chlorogenic acid is below 30%, and the production loss rate of SOD activity is below 20%.

10. A mint throat lozenge tablet, characterized in that: The preparation is obtained by the preparation method according to any one of claims 1 to 9.

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