Stable buccal product based on pH regulator controlled release and preparation method thereof

Abstract

The invention discloses a stable buccal product based on pH regulator controlled release and a preparation method thereof, and relates to the technical field of nicotine buccal product preparation. The buccal product comprises the following components in parts by weight: 1-10 parts of a binder, 1-5 parts of a first filler, 2-5 parts of a wetting agent, 0.2-2 parts of a disintegrating agent, 1-2 parts of a pH regulator, 1-10 parts of nicotine ditartrate salt, 1-10 parts of nicotine resin, 30-50 parts of a second filler, 5-15 parts of a humectant, 0.3-1.5 parts of a sweetening agent, 0.5-5 parts of a cooling agent, 2-10 parts of a flavoring agent, 0.2-4 parts of an antioxidant and 1-5 parts of sodium chloride. And the pH regulator is carbonate. On the basis of the nicotine resin, the nicotine ditartrate salt which is comfortable in mouth feel and quick in head feeling is selected, meanwhile, the pH value of the buccal product powder is adjusted to be 6-6.5, and the technical effects of being stable in storage, free of sour taste, quick in head feeling and comfortable are achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of nicotine oral product preparation, and in particular to a stable oral product based on pH regulator controlled release and a preparation method thereof. Background Art

[0002] Traditional oral products containing nicotine salts generally directly mix pH regulators and nicotine sources. This will lead to the release of free nicotine, resulting in problems such as discoloration and nicotine content attenuation in oral products, and poor head comfort. In addition, traditional oral products containing nicotine salts have a single nicotine source, which is basically resin nicotine salt. Summary of the invention

[0003] The present invention provides a stable oral product based on pH regulator controlled release and a preparation method thereof, wherein nicotine ditartaric acid salt having a comfortable mouthfeel and a rapid head feeling is selected on the basis of resin nicotine salt, the pH of the oral product powder containing resin nicotine and nicotine ditartaric acid salt is adjusted to 6-6.5 in the preparation method, and a pH regulator carbonate coated by a granulation process is added at the same time. The technical effects of stable storage, no sour taste, rapid and comfortable head feeling are achieved.

[0004] The specific technical solutions include the following:

[0005] In a first aspect, a stable oral preparation based on pH regulator controlled release is provided, comprising the following components in parts by weight:

[0006] 1-10 parts of a binder, 1-5 parts of a first filler, 2-5 parts of a wetting agent, 0.2-2 parts of a disintegrant, 1-2 parts of a pH adjuster, 1-10 parts of nicotine ditartrate, 1-10 parts of a nicotine resin, 30-50 parts of a second filler, 5-15 parts of a humectant, 0.3-1.5 parts of a sweetener, 0.5-5 parts of a cooling agent, 2-10 parts of a flavoring agent, 0.2-4 parts of an antioxidant, and 1-5 parts of sodium chloride; the pH adjuster is a carbonate.

[0007] Furthermore, the weight ratio of the nicotine ditartaric acid salt to the nicotine resin is 1:(0.2-4).

[0008] Preferably, the weight portion of the nicotine ditartrate salt is 2-8 parts, and the weight portion of the nicotine resin is 2-8 parts.

[0009] Furthermore, the binder is one or more of gum arabic, methyl cellulose, gelatin, ethyl cellulose, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, and starch; and the first filler is one or more of mannitol, maltitol, and sorbitol.

[0010] Furthermore, the wetting agent is ethanol; and the disintegrant is one or more of sodium alginate, sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose cross-linked polyvinylpyrrolidone.

[0011] Furthermore, the carbonate is one or more of sodium carbonate and potassium carbonate.

[0012] Furthermore, the second filler is one or more of microcrystalline cellulose, maltitol, mannitol, and sorbitol; and the humectant is one or more of glycerol and propylene glycol.

[0013] Furthermore, the sweetener is one or more of acesulfame potassium, sucralose, and neotame; and the cooling agent is one or more of WS-3 and WS-23.

[0014] Furthermore, the flavoring agent is one or more of strawberry flavor, sweet orange flavor, watermelon flavor, lemon flavor, mint flavor, and wintergreen flavor; the antioxidant is one or more of sodium sulfite, sodium thiosulfate, sodium ascorbate, and tea polyphenols.

[0015] Preferably, the stable oral preparation based on controlled release of a pH regulator further comprises a carbonate solution with a mass concentration of 10%, and the carbonate solution is a sodium carbonate solution or a potassium carbonate solution.

[0016] In a second aspect, a method for preparing a stable oral preparation based on controlled release of a pH regulator as described in the first aspect is provided, comprising the following steps:

[0017] S1. The binder, the first filler, the wetting agent, the disintegrant, and the pH adjuster are mixed evenly, kneaded into a mass, the mass mixture is squeezed for a first sieving, and then dried, and after drying, kneaded again for a second sieving to obtain hydrophilic gelatin carbonate particles;

[0018] S2. The second filler, humectant, sweetener, cooling agent, flavoring agent, antioxidant, sodium chloride and water are mixed evenly, and then nicotine ditartaric acid salt and nicotine resin are added and mixed evenly, and a carbonate solution having a mass concentration of 10% is added dropwise so that the pH is 6-6.5 to obtain an oral powder product;

[0019] S3. The hydrophilic gelatin carbonate particles obtained in step S1 are uniformly mixed with the oral preparation powder obtained in step S2, and packed in bags according to 0.55 g to obtain a stable oral preparation based on controlled release of a pH regulator.

[0020] Furthermore, in step S1, the mesh sizes of the first sieving and the second sieving are both 40-50 meshes, and the drying temperature is 50-80°C.

[0021] The present invention provides a stable oral product based on pH regulator controlled release and a preparation method thereof. Nicotine ditartaric acid salt with a comfortable mouthfeel and a quick head feeling is selected on the basis of nicotine resin. At the same time, the pH of the oral product powder is adjusted to 6-6.5 in the preparation method, and hydrophilic gelatin carbonate particles coated with pH regulator by granulation process are added. The hydrophilic gelatin carbonate particles are stable under low humidity conditions and disintegrate under high humidity conditions. The beneficial effects of the present invention are:

[0022] 1) Under storage conditions, the pH of the powder system of the oral product is 6-6.5, free nicotine is not precipitated, and it is not easy to oxidize and deteriorate;

[0023] 2) The stable oral preparation based on pH regulator controlled release has no sour taste when first taken in the mouth;

[0024] 3) The hydrophilic carbonate particles of the pH-adjusting agent-controlled stable oral preparation absorb water and disintegrate rapidly after ingestion, so that the pH of the system reaches between 8 and 9, free nicotine precipitates, and the nicotine is quickly released. DETAILED DESCRIPTION

[0025] 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.

[0026] 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.

[0027] 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.

[0028] 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.

[0029] 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.

[0030] Preparation method of stable oral preparation based on pH regulator controlled release

[0031] S1. The binder, the first filler, the wetting agent, the disintegrant, and the pH adjuster are mixed evenly, kneaded into a mass, the mass mixture is squeezed for a first screening, and then dried, and after drying, kneaded again for a second screening to obtain hydrophilic gelatin carbonate particles; wherein, in step S1, the mesh size of the first screening and the second screening is 40-50 mesh, and the drying temperature is 50-80°C;

[0032] S2. The second filler, humectant, sweetener, cooling agent, flavoring agent, antioxidant, sodium chloride and water are mixed evenly, and then nicotine ditartaric acid salt and nicotine resin are added and mixed evenly, and a carbonate solution having a mass concentration of 10% is added dropwise so that the pH is 6-6.5 to obtain an oral powder product;

[0033] S3. The hydrophilic gelatin carbonate particles obtained in step S1 are uniformly mixed with the oral preparation powder obtained in step S2, and packed in bags according to 0.55 g to obtain a stable oral preparation based on controlled release of a pH regulator.

[0034] Performance Testing

[0035] 120h Nicotine retention rate (%): Nicotine retention rate was measured after accelerated oxidation for 120h in a constant temperature and humidity chamber at 60°C and 90% humidity.

[0036] Nicotine release pattern test: The steroid method is used to determine the nicotine release pattern. 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.

[0037] Sensory description: Observe whether the sample turns yellow after the 120-hour nicotine retention test. When testing the nicotine release pattern, test the sourness, irritation, speed of getting high, and comfort of the oral product.

[0038] Example

[0039] Example 1

[0040] A stable oral preparation based on pH regulator controlled release, comprising the following components in parts by weight:

[0041] 6.3 parts of binder (consisting of 5g polyvinyl pyrrolidone and 1.3g starch), 2 parts of wetting agent (2mL of 95% ethanol by volume), 5 parts of first filler (5g mannitol), 0.2 parts of disintegrant (0.2g sodium alginate), 1 part of pH adjuster (1g sodium carbonate), 2 parts (2g) of nicotine ditartrate, 8 parts (8g) of nicotine resin, 40 parts of second filler (40g microcrystalline cellulose), 10 parts of humectant (10g propylene glycol), 0.6 parts of sweetener (consisting of 0.5g acesulfame potassium and 0.1g sucralose), 2 parts of cooling agent (2g WS-23), 10 parts of flavoring agent (10g strawberry flavor), 2 parts of antioxidant (2g sodium ascorbate), 2 parts (2g) of sodium chloride, and also including 10% sodium carbonate solution by mass.

[0042] The method for preparing a stable oral preparation based on pH regulating agent controlled release of Example 1 comprises the following steps:

[0043] S1. The binder, the first filler, the wetting agent, the disintegrant, and the pH adjuster are mixed evenly, kneaded into a mass, and the mass mixture is squeezed for a first sieving, the first sieving mesh is 50 mesh, and then dried, the drying temperature is 70 ° C, the drying time is 30min, and after drying, the second sieving mesh is 50 mesh, and the hydrophilic gel carbonate particles are obtained;

[0044] S2. The second filler, humectant, sweetener, cooling agent, flavoring agent, antioxidant, sodium chloride and water are mixed evenly, and then nicotine ditartaric acid salt and nicotine resin are added and mixed evenly, and a sodium carbonate solution having a mass concentration of 10% is added dropwise so that the pH is 6.2 to obtain an oral powder product;

[0045] S3. The hydrophilic gelatin carbonate particles obtained in step S1 are uniformly mixed with the oral preparation powder obtained in step S2, and packed in bags according to 0.55 g to obtain a stable oral preparation based on controlled release of a pH regulator.

[0046] Example 2

[0047] A stable oral preparation based on pH regulator controlled release, comprising the following components in parts by weight:

[0048] 6.3 parts of binder (consisting of 5g polyvinyl pyrrolidone and 1.3g starch), 2 parts of wetting agent (2mL of 95% ethanol by volume), 5 parts of first filler (5g mannitol), 0.2 parts of disintegrant (0.2g sodium alginate), 1 part of pH regulator (1g sodium carbonate), 4 parts of nicotine ditartrate (4g), 6 parts of nicotine resin (6g), 40 parts of second filler (40g microcrystalline cellulose), 10 parts of humectant (10g propylene glycol), 0.6 parts of sweetener (consisting of 0.5g acesulfame potassium and 0.1g sucralose), 2 parts of cooling agent (2g WS-23), 10 parts of flavoring agent (10g strawberry flavor), 2 parts of antioxidant (2g sodium ascorbate), 2 parts of sodium chloride (2g), and also including 10% sodium carbonate solution by mass.

[0049] Example 3

[0050] A stable oral preparation based on pH regulator controlled release, comprising the following components in parts by weight:

[0051] 6.3 parts of binder (consisting of 5g polyvinyl pyrrolidone and 1.3g starch), 2 parts of wetting agent (2mL of 95% ethanol by volume), 5 parts of first filler (5g mannitol), 0.2 parts of disintegrant (0.2g sodium alginate), 1 part of pH regulator (1g sodium carbonate), 6 parts (6g) of nicotine ditartrate, 4 parts (4g) of nicotine resin, 40 parts of second filler (40g microcrystalline cellulose), 10 parts of humectant (10g propylene glycol), 0.6 parts of sweetener (consisting of 0.5g acesulfame potassium and 0.1g sucralose), 2 parts of cooling agent (2g WS-23), 10 parts of flavoring agent (10g strawberry flavor), 2 parts of antioxidant (2g sodium ascorbate), 2 parts of sodium chloride (2g), and also including 10% sodium carbonate solution by mass.

[0052] Example 4

[0053] A stable oral preparation based on pH regulator controlled release, comprising the following components in parts by weight:

[0054] 6.3 parts of binder (consisting of 5g polyvinyl pyrrolidone and 1.3g starch), 2 parts of wetting agent (2mL of 95% ethanol by volume), 5 parts of first filler (5g mannitol), 0.2 parts of disintegrant (0.2g sodium alginate), 1 part of pH regulator (1g sodium carbonate), 8 parts (8g) of nicotine ditartrate, 2 parts (2g) of nicotine resin, 40 parts of second filler (40g microcrystalline cellulose), 10 parts of humectant (10g propylene glycol), 0.6 parts of sweetener (consisting of 0.5g acesulfame potassium and 0.1g sucralose), 2 parts of cooling agent (2g WS-23), 10 parts of flavoring agent (10g strawberry flavor), 2 parts of antioxidant (2g sodium ascorbate), 2 parts (2g) of sodium chloride, and also including 10% sodium carbonate solution by mass.

[0055] The preparation methods of the stable oral preparations based on pH adjusting agent controlled release in Examples 2-4 are the same as that in Example 1.

[0056] Comparative Example 1

[0057] The difference between Comparative Example 1 and Example 1 is that there is no disintegrant (sodium alginate) in the stable oral preparation based on pH regulator controlled release, and the other conditions are the same.

[0058] Comparative Example 2

[0059] The difference between Comparative Example 2 and Example 1 is that there is no binder in the stable oral preparation based on pH regulator controlled release, and the other conditions are the same.

[0060] Comparative Example 3

[0061] Compared with Example 1, Comparative Example 3 differs in that in the method for preparing a stable oral product based on controlled release of a pH regulator, step S2 is to drip a sodium carbonate solution with a mass concentration of 10% to make the pH at 4.5, and the other conditions are the same.

[0062] Comparative Example 4

[0063] Compared with Example 1, Comparative Example 4 differs in that in the method for preparing a stable oral product based on controlled release of a pH regulator, step S2 is to drip a sodium carbonate solution with a mass concentration of 10% to make the pH at 5.5, and the other conditions are the same.

[0064] Comparative Example 5

[0065] Compared with Example 1, Comparative Example 5 differs in that in the method for preparing a stable oral product based on controlled release of a pH regulator, step S2 is to drip a sodium carbonate solution with a mass concentration of 10% to make the pH at 7.5, and the other conditions are the same.

[0066] Comparative Example 6

[0067] Compared with Example 1, Comparative Example 4 differs in that in the method for preparing a stable oral product based on controlled release of a pH regulator, step S2 is to drip a sodium carbonate solution with a mass concentration of 10% to make the pH at 9.5, and the other conditions are the same.

[0068] Comparative Example 7

[0069] Compared with Example 1, Comparative Example 7 differs in that the weight portion of nicotine ditartrate salt in the stable oral preparation based on pH regulator controlled release is 0.1 parts (0.1 g), and the weight portion of nicotine resin is 10 parts (10 g), that is, the weight ratio of nicotine ditartrate salt to nicotine resin is 0.1:10, and the other conditions are the same.

[0070] Comparative Example 8

[0071] Compared with Example 1, Comparative Example 8 differs in that the weight portion of nicotine ditartrate salt in the stable oral preparation based on pH regulator controlled release is 10 parts (10 g), and the weight portion of nicotine resin is 0.1 parts (g), that is, the weight ratio of nicotine ditartrate salt to nicotine resin is 1:0.1, and the other conditions are the same.

[0072] Comparative Example 9

[0073] The difference between Comparative Example 9 and Example 1 is that the same weight portions of pH adjuster (sodium carbonate) are used to replace the binder, the first filler, the wetting agent and the disintegrant, and the other conditions are the same.

[0074] Comparative Example 10

[0075] The difference between Comparative Example 10 and Example 1 is that in the preparation method of the stable oral preparation based on pH regulator controlled release, step S1 is to mix the binder, the first filler, the wetting agent, the disintegrant, and the pH regulator evenly, knead them into a mass, squeeze the mass mixture and sieve it, the mesh number of the sieve is 50 mesh, and then dry it, and no second sieving is performed to obtain the hydrophilic gum carbonate particles, and the other conditions are the same.

[0076] The performance tests were conducted on the stable oral preparations based on pH regulator controlled release of Examples 1-4. The test structure is shown in Table 1 below:

[0077] Table 1 Performance test results of stable oral preparations based on pH regulator controlled release in Examples 1-4

[0078]

[0079]

[0080] In addition, the pH value of the stable oral preparations based on pH regulator controlled release of Examples 1-4 is about 8.6 when used. From the test results in Table 1, it can be seen that, based on Examples 1-4, the nicotine in the stable oral preparations based on pH regulator controlled release prepared by the method of the present invention is stable, not easy to change color, has no sour taste, and has a quick and comfortable feeling of being on the head; because the combination of nicotine and resin is stronger than tartaric acid, the nicotine release rate can be controlled by changing the weight ratio of tartaric acid nicotine salt to nicotine resin. The stable oral preparations based on pH regulator controlled release of Comparative Examples 1-10 were subjected to performance tests, and the test structure is shown in Table 2 below:

[0081] Table 2 Performance test results of stable oral preparations based on pH regulator controlled release in comparative examples 1-10

[0082]

[0083]

[0084] It can be seen from the test results in Table 2 that the disintegration of the hydrophilic gel carbonate particles in the present invention depends on sodium alginate (disintegrant), and the bonding depends on starch (binder). If there is too little sodium alginate (Comparative Example 1), the sodium carbonate in the hydrophilic gel carbonate particles will precipitate, resulting in an increase in the pH of the nicotine salt system, making nicotine easy to change color and unstable. If there is too little starch (Comparative Example 2), the sodium carbonate in the hydrophilic gel carbonate particles will not be able to disintegrate, and the pH of the nicotine salt system will not be able to increase, resulting in a poor sense of the head. In addition, when the pH value of the oral product powder in the preparation process of a stable oral product based on the controlled release of a pH regulator is too low (Comparative Example 3, Comparative Example 4), although the nicotine salt will be more stable, it is easy to cause a sour taste and a poor experience; the final pH is too high, which will cause the alkaline burning sensation on the lips to become stronger.

[0085] In addition, if the weight ratio of nicotine ditartaric acid salt to nicotine resin is not within the range defined in the present invention, the performance test results of the stable oral products based on pH regulator controlled release (Comparative Example 7, Comparative Example 8) obtained therefrom are poor. If a pH regulator is used to replace the binder, the first filler, the wetting agent and the disintegrant in the components, the performance test results of the stable oral products based on pH regulator controlled release (Comparative Example 9) obtained therefrom are poor. If different steps are used in the preparation method to prepare hydrophilic gel carbonate particles, the performance test results of the stable oral products based on pH regulator controlled release (Comparative Example 10) obtained therefrom are poor.

[0086] In summary, the stable oral preparation based on pH regulator controlled release and the preparation method thereof provided by the present invention have the following beneficial effects:

[0087] 1) Under storage conditions, the pH of the powder system of the oral product is 6-6.5, free nicotine is not precipitated, and it is not easy to oxidize and deteriorate;

[0088] 2) The stable oral preparation based on pH regulator controlled release has no sour taste when first taken in the mouth;

[0089] 3) The hydrophilic carbonate particles of the pH-adjusting agent-controlled stable oral preparation absorb water and disintegrate rapidly after ingestion, so that the pH of the system reaches between 8 and 9, free nicotine precipitates, and the nicotine is quickly released.

[0090] 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 stable oral product based on pH regulator controlled release, characterized in that: It comprises the following components in parts by weight: 1-10 parts of a binder, 1-5 parts of a first filler, 2-5 parts of a wetting agent, 0.2-2 parts of a disintegrant, 1-2 parts of a pH adjuster, 1-10 parts of nicotine ditartrate, 1-10 parts of a nicotine resin, 30-50 parts of a second filler, 5-15 parts of a humectant, 0.3-1.5 parts of a sweetener, 0.5-5 parts of a cooling agent, 2-10 parts of a flavoring agent, 0.2-4 parts of an antioxidant, and 1-5 parts of sodium chloride; the pH adjuster is a carbonate.

2. The stable oral preparation based on pH adjusting agent controlled release according to claim 1, characterized in that: The weight ratio of the nicotine ditartaric acid salt to the nicotine resin is 1:(0.2-4).

3. The stable oral preparation based on pH adjusting agent controlled release according to claim 1, characterized in that: The binder is one or more of gum arabic, methyl cellulose, gelatin, ethyl cellulose, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, and starch; the first filler is one or more of mannitol, maltitol, and sorbitol.

4. The stable oral preparation based on pH adjusting agent controlled release according to claim 1, characterized in that: The wetting agent is ethanol; the disintegrant is one or more of sodium alginate, sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose cross-linked polyvinylpyrrolidone.

5. The stable oral preparation based on pH adjusting agent controlled release according to claim 1, characterized in that: The carbonate is one or more of sodium carbonate and potassium carbonate.

6. The stable oral preparation based on pH adjusting agent controlled release according to claim 1, characterized in that: The second filler is one or more of microcrystalline cellulose, maltitol, mannitol, and sorbitol; the humectant is one or more of glycerol and propylene glycol.

7. The stable oral preparation based on pH adjusting agent controlled release according to claim 1, characterized in that: The sweetener is one or more of acesulfame potassium, sucralose, and neotame; the cooling agent is one or more of WS-3 and WS-23.

8. The stable oral preparation based on pH adjusting agent controlled release according to claim 1, 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; the antioxidant is one or more of sodium sulfite, sodium thiosulfate, sodium ascorbate, and tea polyphenols.

9. The method for preparing a stable oral product based on controlled release of a pH regulator according to any one of claims 1 to 8, characterized in that: The following steps are involved: S1. The binder, the first filler, the wetting agent, the disintegrant, and the pH adjuster are mixed evenly, kneaded into a mass, the mass mixture is squeezed for a first sieving, and then dried, and after drying, kneaded again for a second sieving to obtain hydrophilic gelatin carbonate particles; S2. The second filler, humectant, sweetener, cooling agent, flavoring agent, antioxidant, sodium chloride and water are mixed evenly, and then nicotine ditartaric acid salt and nicotine resin are added and mixed evenly, and a carbonate solution having a mass concentration of 10% is added dropwise so that the pH is 6-6.5 to obtain an oral powder product; S3. The hydrophilic gelatin carbonate particles obtained in step S1 are uniformly mixed with the oral preparation powder obtained in step S2, and packed in bags according to 0.55 g to obtain a stable oral preparation based on controlled release of a pH regulator.

10. The method for preparing a stable oral product based on controlled release of a pH regulator according to claim 9, characterized in that: In step S1, the mesh sizes of the first sieving and the second sieving are both 40-50 meshes, and the drying temperature is 50-80°C.

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