Sustained-release granules containing gamma-aminobutyric acid as well as preparation method and application of sustained-release granules

Abstract

The invention provides sustained-release granules containing gamma-aminobutyric acid as well as a preparation method and application of the sustained-release granules, and relates to the technical field of sustained release. The invention discloses a GABA sustained-release particle prepared by compounding glyceride and vegetable wax with gamma-aminobutyric acid for the first time, particularly provides a structure of the GABA sustained-release particle, and provides a preparation method of the GABA sustained-release particle by taking glyceride, vegetable wax and gamma-aminobutyric acid as a core material and taking glyceride and vegetable wax as a coating to wrap the core material. The GABA sustained-release granules are simple in components and production process, and large-scale industrial production can be realized. Use of hazardous chemicals and chemical reactions are not involved, and no pollution is caused to the environment; the product has small particle size, can meet the use requirements of various medicines, health care products, foods or cosmetics, and has guiding significance for development of GABA food-grade sustained-release products and other sustained-release products.

Description

Technical Field

[0001] This application relates to the field of sustained-release technology, and particularly relates to a sustained-release granule containing γ-aminobutyric acid, its preparation method and application. Background Art

[0002] γ-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system. It is a naturally occurring non-proteinogenic amino acid with extremely important physiological functions. It can promote brain activation, enhance intelligence, anti-epileptic, promote sleep, repair wrinkles, beautify the skin, delay brain aging function, can supplement the body's inhibitory neurotransmitter, has a good blood pressure lowering effect, promotes kidney function improvement and protection, inhibits fatty liver and obesity, and activates liver function. Daily supplementation of trace amounts of GABA is beneficial to the relief of heart and brain blood pressure, regulates immune function, and improves the skin. In short, GABA has been widely used in the fields of food, cosmetics, and pharmaceuticals, etc.

[0003] GABA has strong water solubility and can be quickly absorbed by the human body as a small molecule non-protein amino acid. Therefore, it cannot achieve long-term release and has a short action time. And after being quickly absorbed by the human body, GABA may cause symptoms such as increased heart rate, rapid breathing, headache, nausea, diarrhea, etc. In severe cases, it may even produce a central inhibitory effect on the nervous system, causing the taker to experience nerve fatigue, dullness, coma, drowsiness, etc.

[0004] CN115919806A discloses a preparation method of a GABA sustained-release capsule. After wet granulation, it is coated with enteric coating and then filled into a capsule shell. The matrix materials include lactose, microcrystalline cellulose, and hydroxypropyl methylcellulose, and the coating material is mainly Eudragit L30D-55. However, the GABA content in this capsule is relatively low. If the GABA content is increased, the addition amount of excipients such as hydroxypropyl methylcellulose is limited in food applications.

[0005] Therefore, there is an urgent need for a GABA sustained-release granule with high safety and good sustained-release effect. Summary of the Invention

[0006] The purpose of the present invention is to provide a sustained-release granule containing γ-aminobutyric acid with both safety and sustained-release effect, and provide its preparation method and application.

[0007] On the one hand, this application provides a sustained-release granule containing γ-aminobutyric acid, which is characterized in that the sustained-release granule includes γ-aminobutyric acid and a matrix material, and the matrix material includes at least glyceride and plant wax.

[0008] On the other hand, the present application provides a sustained-release granule containing γ-aminobutyric acid. The sustained-release granule includes a core material and a coating; the core material includes γ-aminobutyric acid and a skeleton material, and the skeleton material includes glycerol ester and / or plant wax; the coating includes glycerol ester and / or plant wax.

[0009] Further, the coating includes glycerol ester and plant wax.

[0010] Further, the glycerol ester includes one or more of glycerol monostearate, glycerol distearate, and glyceryl behenate; preferably, glycerol monostearate.

[0011] Preferably, the glycerol ester in the skeleton material includes one or more of glycerol monostearate, glycerol distearate, and glyceryl behenate; preferably, glycerol monostearate.

[0012] Preferably, the glycerol ester in the coating includes one or more of glycerol monostearate, glycerol distearate, and glyceryl behenate; preferably, glycerol monostearate.

[0013] Further, the plant wax includes one or more of carnauba wax, rice bran wax, and candelilla wax; preferably, carnauba wax.

[0014] Preferably, the plant wax in the skeleton material includes one or more of carnauba wax, rice bran wax, and candelilla wax; preferably, carnauba wax.

[0015] Preferably, the plant wax in the coating includes one or more of carnauba wax, rice bran wax, and candelilla wax; preferably, carnauba wax.

[0016] Further, the mass ratio of glycerol ester to plant wax in the skeleton material is (0.1 - 3):1.

[0017] Among them, the mass ratio of glycerol ester to plant wax in the skeleton material can be any value among 0.1:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1:1, 1.5:1, 2:1, 2.5:1, 3:1.

[0018] Preferably, the mass ratio of glycerol ester to plant wax in the skeleton material is (1 - 3):1.

[0019] Further, the mass ratio of glycerol ester to plant wax in the coating is (0.1 - 3):1.

[0020] Among them, the mass ratio of glyceride to vegetable wax in the coating can be any value among 0.1:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1:1, 1.5:1, 2:1, 2.5:1, 3:1.

[0021] Preferably, the mass ratio of glyceride to vegetable wax in the coating is (0.5 - 2):1.

[0022] Furthermore, the mass ratio of γ-aminobutyric acid to the matrix material is (100 - 140):(20 - 80).

[0023] Among them, the mass ratio of γ-aminobutyric acid to the matrix material can be any value among 100:20, 110:20, 120:20, 130:20, 140:20, 100:30, 110:30, 120:30, 130:30, 140:30, 100:40, 110:40, 120:40, 130:40, 140:40, 100:50, 110:50, 120:50, 130:50, 140:50, 100:60, 110:60, 120:60, 130:60, 140:60, 100:70, 110:70, 120:70, 130:70, 140:70, 100:80, 110:80, 120:80, 130:80, 140:80.

[0024] Preferably, (110 - 130):(30 - 50).

[0025] Furthermore, by mass percentage, the γ-aminobutyric acid accounts for 40% - 80% of the total mass of the sustained-release granules.

[0026] Among them, by mass percentage, the γ-aminobutyric acid can account for any value among 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80% of the total mass of the sustained-release granules.

[0027] Preferably, the γ-aminobutyric acid accounts for 50 - 70% of the total mass of the sustained-release granules.

[0028] More preferably, the γ-aminobutyric acid accounts for 60% of the total mass of the sustained-release granules.

[0029] Further, by mass percentage, the skeleton material may account for 60%-10% of the total mass of the sustained-release granules.

[0030] Further, the skeleton material may account for any value among 60%, 50%, 40%, 30%, 20%, and 10% of the total mass of the sustained-release granules.

[0031] Preferably, 20%.

[0032] Further, by mass percentage, the core material accounts for 40%-90% of the total mass of the sustained-release granules.

[0033] Among them, by mass percentage, the core material may account for any value among 40%, 50%, 60%, 70%, 80%, and 90% of the total mass of the sustained-release granules.

[0034] Preferably, 80%.

[0035] Further, by mass percentage, the coating accounts for 60%-10% of the total mass of the sustained-release granules.

[0036] Among them, by mass percentage, the coating may account for any value among 60%, 50%, 40%, 30%, 20%, and 10% of the total mass of the sustained-release granules.

[0037] Preferably, 20%.

[0038] In a preferred embodiment, the sustained-release granules include a core material and a coating; the core material includes γ-aminobutyric acid and a skeleton material with a mass ratio of (100-140):(20-80), and the skeleton material includes glycerol monostearate and carnauba wax with a mass ratio of (0.1-3):1; the coating includes glycerol monostearate and carnauba wax with a mass ratio of (0.1-3):1, and the core material accounts for 40%-90% of the total mass of the sustained-release granules.

[0039] In a preferred embodiment, the sustained-release granules include a core material and a coating; the core material includes γ-aminobutyric acid and a skeleton material with a mass ratio of 120:40, the skeleton material includes glycerol monostearate and carnauba wax with a mass ratio of 5:3; the coating includes glycerol monostearate and carnauba wax with a mass ratio of 1:1, and the core material accounts for 80% of the total mass of the sustained-release granules.

[0040] On the other hand, the present application also provides a preparation method of the sustained-release granules, and the method includes the following steps:

[0041] Step 1: Take glycerides and vegetable wax, heat them to melt, add γ-aminobutyric acid and mix to form solid particles to obtain intermediate particles;

[0042] Step 2: Heat the glyceride and vegetable wax until melted to obtain the coating material;

[0043] Step 3: Coat the intermediate particles with the coating material.

[0044] Among them, the heating temperature can be selected according to the actual situation as long as the material can be melted, and the present application does not make specific restrictions on this.

[0045] Furthermore, the step 1 further includes a step of heat preservation at 45°C - 55°C.

[0046] Preferably, after adding γ-aminobutyric acid in step 1, there is also a step of heat preservation, and the temperature condition for heat preservation is 45°C - 55°C.

[0047] The temperature condition for heat preservation can be selected from any value among 45°C, 46°C, 47°C, 48°C, 49°C, 50°C, 51°C, 52°C, 53°C, 54°C, 55°C.

[0048] Preferably, 50°C.

[0049] This step can ensure that the glyceride, vegetable wax and γ-aminobutyric acid do not solidify during the preparation of the solid particles.

[0050] Furthermore, the step 1 further includes a sieving step. Preferably, the mesh number of the sieve for sieving is 20 - 60 meshes.

[0051] Preferably, the mesh number of the sieve for sieving can be any value among 20, 30, 40, 50, 60 meshes.

[0052] Preferably, 40 meshes.

[0053] Within the above preferred mesh number range, the residues and powders in the solid particles can be effectively sieved out, and the complete particles are retained, that is, the intermediate particles are obtained, avoiding excessive powder components in the subsequent preparation process and ensuring the final sustained release effect.

[0054] Among them, the shape of the intermediate particles can be adjusted according to actual needs.

[0055] Those skilled in the art can understand that a general coating method or coating equipment can be used for coating. The coating method can be selected from one or more of the pan coating method, compression coating method, fluidized bed coating method. In a preferred embodiment, the fluidized bed coating method is used for coating.

[0056] The thickness and shape of the coating can also be adjusted according to the actual situation, and the present application does not make specific restrictions.

[0057] Furthermore, the conditions for coating include: the cooling temperature is 25°C - 35°C;

[0058] The coating time is greater than or equal to 40 min.

[0059] Among them, the cooling temperature can be any value among 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C.

[0060] Preferably, the cooling temperature is 30°C and the coating time is 40 min.

[0061] In a preferred embodiment, the method for preparing the sustained-release granules includes the following steps:

[0062] Step 1: Take glyceryl monostearate and carnauba wax, heat to melt, add γ-aminobutyric acid, mix and keep warm at 45°C - 55°C to form solid granules, and sieve to obtain intermediate granules;

[0063] Step 2: Heat glyceryl monostearate and carnauba wax to melt to obtain a coating material;

[0064] Step 3: Coat the intermediate granules with the coating material.

[0065] On the other hand, the present application also provides the application of the above method in improving the slow-release effect of γ-aminobutyric acid.

[0066] Preferably, the slow release is achieved in the human digestive system.

[0067] On the other hand, the present application also provides the application of the above sustained-release granules or the above method in the preparation of drugs, foods and / or cosmetics containing γ-aminobutyric acid.

[0068] Preferably, the drug is an oral preparation.

[0069] The present invention has the following beneficial effects:

[0070] In the present invention, for the first time, it is disclosed that γ-aminobutyric acid is compounded with glycerol ester and plant wax to prepare GABA sustained-release granules. Specifically, a structure of a GABA sustained-release granule is also given, including using glycerol ester, plant wax and γ-aminobutyric acid mixed as the core material, and using glycerol ester and plant wax as the coating to wrap the core material, and a preparation method of the GABA sustained-release granule is given. The GABA sustained-release granules prepared by this method have a good slow-release effect, especially can achieve slow release in the human digestive system.

[0071] In the present invention, the composition and production process of the GABA sustained-release granules are simple, enabling large-scale industrial production. Moreover, it does not involve the use of hazardous chemicals or chemical reactions, causing no pollution to the environment. Compared with the existing capsules, the product has a small particle size, meeting the usage requirements of various foods, and can be used in the fields of pharmaceuticals, foods, or cosmetics, which is of guiding significance for the development of GABA food-grade sustained-release products and other sustained-release products. Detailed Embodiments

[0072] In order to more clearly illustrate the overall concept of the present application, the following will be described in detail by way of examples. In the following description, a large number of specific details are given to provide a more thorough understanding of the present invention. However, it is obvious to those skilled in the art that the present invention can be implemented without one or more of these details. In other examples, in order to avoid confusion with the present invention, some well-known technical features in the art are not described.

[0073] It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present application belongs.

[0074] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0075] Unless otherwise specified, in the following embodiments, the reagents or instruments without indicating the manufacturer can be obtained as conventional products through commercial purchase.

[0076] Among them, the CAS number of glycerol monostearate is: 123-94-4, the CAS number of carnauba wax is: 8015-86-9, and the CAS number of γ-aminobutyric acid is: 56-12-2.

[0077] Before further describing the specific embodiments of the present invention, it should be understood that the protection scope of the present invention is not limited to the specific embodiments described below; it should also be understood that the terms used in the embodiments of the present invention are for describing specific embodiments and not for limiting the protection scope of the present invention. The test methods without specifying specific conditions in the following examples are generally carried out under conventional conditions or according to the conditions recommended by each manufacturer.

[0078] When numerical ranges are given in the examples, it should be understood that unless otherwise specified in the present invention, both endpoints of each numerical range and any value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those skilled in the art of this technology. In addition to the specific methods, equipment, and materials used in the examples, according to the knowledge of those skilled in the art of this technology and the description of the present invention, any methods, equipment, and materials of the prior art similar to or equivalent to those described in the examples of the present invention can also be used to implement the present invention.

[0079] Unless otherwise specified, the experimental methods, detection methods, and preparation methods disclosed in the present invention all adopt the conventional techniques in the fields of microbiology, biochemistry, analytical chemistry, cell culture, and related fields in this technology.

[0080] In addition, the "water" mentioned in the present invention includes any feasible water that can be used in this field, such as deionized water, distilled water, ion-exchanged water, double-distilled water, high-purity water, purified water, etc.

[0081] In the following examples, unless otherwise specifically stated, % represents wt%, that is, weight percentage.

[0082] Example 1

[0083] This example provides a preparation method of GABA sustained-release granules, which includes the following steps:

[0084] (1) Take 60 parts of glyceryl monostearate and 20 parts of carnauba wax, heat them to the molten state, mix 120 parts of GABA with the above liquid evenly to obtain material a, and keep it at 50 °C.

[0085] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a swing granulator to size it to make solid granules, obtaining material b.

[0086] (3) Screen material b with a 40-mesh sieve to remove waste residues, and then cool it to room temperature to obtain material c (GABA sustained-release granules).

[0087] Example 2

[0088] This example provides a preparation method of GABA sustained-release granules, which includes the following steps:

[0089] (1) Take 50 parts of glyceryl monostearate and 30 parts of carnauba wax, heat them to the molten state, mix 120 parts of GABA with the above liquid evenly to obtain material a, and keep it at 50 °C.

[0090] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a rocking granulator to size it to form solid particles, obtaining material b;

[0091] (3) Screen out the waste residue from material b using a 40-mesh sieve and then cool it to room temperature to obtain material c (GABA sustained-release granules).

[0092] Example 3

[0093] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0094] (1) Take 40 parts of glycerol monostearate and 40 parts of carnauba wax, heat them to a molten state, mix 120 parts of GABA evenly with the above liquid to obtain material a, and keep it at 50 °C;

[0095] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a rocking granulator to size it to form solid particles, obtaining material b;

[0096] (3) Screen out the waste residue from material b using a 40-mesh sieve and then cool it to room temperature to obtain material c (GABA sustained-release granules).

[0097] Example 4

[0098] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0099] (1) Take 30 parts of glycerol monostearate and 50 parts of carnauba wax, heat them to a molten state, mix 120 parts of GABA evenly with the above liquid to obtain material a, and keep it at 50 °C;

[0100] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a rocking granulator to size it to form solid particles, obtaining material b;

[0101] (3) Screen out the waste residue from material b using a 40-mesh sieve and then cool it to room temperature to obtain material c (GABA sustained-release granules).

[0102] Example 5

[0103] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0104] (1) Take 20 parts of glycerol monostearate and 60 parts of carnauba wax, heat them to a molten state, mix 120 parts of GABA evenly with the above liquid to obtain material a, and keep it at 50 °C;

[0105] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a swing granulator to perform sizing to make solid granules, obtaining material b;

[0106] (3) Screen out the waste residue from material b using a 40-mesh sieve and cool it to room temperature to obtain material c (GABA sustained-release granules).

[0107] Example 6

[0108] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0109] (1) Take 50 parts of glyceryl behenate and 30 parts of carnauba wax, heat them to a molten state, mix 120 parts of GABA evenly with the above liquid to obtain material a, and keep it at 50 °C;

[0110] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a swing granulator to perform sizing to make solid granules, obtaining material b;

[0111] (3) Screen out the waste residue from material b using a 40-mesh sieve and cool it to room temperature to obtain material c (GABA sustained-release granules).

[0112] Example 7

[0113] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0114] (1) Take 50 parts of diglycerol distearate and 30 parts of carnauba wax, heat them to a molten state, mix 120 parts of GABA evenly with the above liquid to obtain material a, and keep it at 50 °C;

[0115] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a swing granulator to perform sizing to make solid granules, obtaining material b;

[0116] (3) Screen out the waste residue from material b using a 40-mesh sieve and cool it to room temperature to obtain material c (GABA sustained-release granules).

[0117] Example 8

[0118] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0119] (1) Take 50 parts of glyceryl monostearate and 30 parts of rice bran wax, heat them to a molten state, mix 120 parts of GABA evenly with the above liquid to obtain material a, and keep it at 50 °C;

[0120] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, and after cooling to room temperature, use a rocking granulator to perform granulation to make solid particles, obtaining material b;

[0121] (3) Use a 40-mesh sieve to screen out the waste residue from material b and then cool it to room temperature to obtain material c (GABA sustained-release granules).

[0122] Example 9

[0123] This example provides a method for preparing GABA sustained-release granules, including the following steps:

[0124] (1) Take 50 parts of glyceryl monostearate and 30 parts of candelilla wax, heat to the molten state, mix 120 parts of GABA evenly with the above liquid to obtain material a, and keep it at 50 °C;

[0125] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, and after cooling to room temperature, use a rocking granulator to perform granulation to make solid particles, obtaining material b;

[0126] (3) Use a 40-mesh sieve to screen out the waste residue from material b and then cool it to room temperature to obtain material c (GABA sustained-release granules).

[0127] Example 10

[0128] This example provides a method for preparing GABA sustained-release granules, including the following steps:

[0129] (1) Take 50 parts of glyceryl monostearate, heat to the molten state, mix 120 parts of GABA evenly with the above liquid to obtain material a, and keep it at 50 °C;

[0130] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, and after cooling to room temperature, use a rocking granulator to perform granulation to make solid particles, obtaining material b;

[0131] (3) Use a 40-mesh sieve to screen out the waste residue from material b and then cool it to room temperature to obtain material c (GABA sustained-release granules).

[0132] Example 11

[0133] This example provides a method for preparing GABA sustained-release granules, including the following steps:

[0134] (1) Take 30 parts of carnauba wax, heat to the molten state, mix 120 parts of GABA evenly with the above liquid to obtain material a, and keep it at 50 °C;

[0135] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a rocking granulator to size it to form solid granules, obtaining material b;

[0136] (3) Screen out the waste residue from material b using a 40-mesh sieve and then cool it to room temperature to obtain material c (GABA sustained-release granules).

[0137] Example 12

[0138] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0139] (1) Take 25 parts of glyceryl monostearate and 15 parts of carnauba wax, heat them to a molten state, mix 120 parts of GABA evenly with the liquid to obtain material a, and keep it at 50 °C;

[0140] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a rocking granulator to size it to form solid granules, obtaining material b;

[0141] (3) Screen out the waste residue from material b using a 40-mesh sieve to obtain material c;

[0142] (4) Put material c into the granulation chamber of a fluidized bed coater, heat 10 parts of glyceryl monostearate and 30 parts of carnauba wax to a molten state, spray them into the coater through a liquid spraying gun, coat material c, set the cooling temperature at 30 °C, and the coating time at 40 min. After cooling to room temperature, GABA sustained-release granules are obtained.

[0143] Example 13

[0144] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0145] (1) Take 25 parts of glyceryl monostearate and 15 parts of carnauba wax, heat them to a molten state, mix 120 parts of GABA evenly with the liquid to obtain material a, and keep it at 50 °C;

[0146] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a rocking granulator to size it to form solid granules, obtaining material b;

[0147] (3) Screen out the waste residue from material b using a 40-mesh sieve to obtain material c;

[0148] (4) The material c is placed into the granulation chamber of a fluidized bed coater. 15 parts of glyceryl monostearate and 25 parts of carnauba wax are heated to a molten state and sprayed into the coater through a liquid spraying gun to coat the material c. The cooling temperature is set at 30 °C and the coating time is 40 min. After cooling to room temperature, GABA sustained-release granules are obtained.

[0149] Example 14

[0150] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0151] (1) Take 25 parts of glyceryl monostearate and 15 parts of carnauba wax, heat them to a molten state, mix 120 parts of GABA evenly with a liquid to obtain material a, and keep it at 50 °C.

[0152] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a swing granulator to size it to form solid granules, obtaining material b.

[0153] (3) Screen material b with a 40-mesh sieve to remove waste residues to obtain material c.

[0154] (4) The material c is placed into the granulation chamber of a fluidized bed coater. 20 parts of glyceryl monostearate and 20 parts of carnauba wax are heated to a molten state and sprayed into the coater through a liquid spraying gun to coat the material c. The cooling temperature is set at 30 °C and the coating time is 40 min. After cooling to room temperature, GABA sustained-release granules are obtained.

[0155] Example 15

[0156] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0157] (1) Take 25 parts of glyceryl monostearate and 15 parts of carnauba wax, heat them to a molten state, mix 120 parts of GABA evenly with a liquid to obtain material a, and keep it at 50 °C.

[0158] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a swing granulator to size it to form solid granules, obtaining material b.

[0159] (3) Screen material b with a 40-mesh sieve to remove waste residues to obtain material c.

[0160] (4) The material c is placed into the granulation chamber of a fluidized bed coater. 25 parts of glyceryl monostearate and 15 parts of carnauba wax are heated to a molten state and sprayed into the coater through a liquid spraying gun to coat the material c. The cooling temperature is set at 30 °C and the coating time is 40 min. After cooling to room temperature, GABA sustained-release granules are obtained.

[0161] Example 16

[0162] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0163] (1) Take 25 parts of glyceryl monostearate and 15 parts of carnauba wax, heat them to the molten state, mix 120 parts of GABA evenly with the liquid to obtain material a, and keep it at 50 °C;

[0164] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a rocking granulator to size it to form solid granules, obtaining material b;

[0165] (3) Screen material b with a 40-mesh sieve to remove waste residue to obtain material c;

[0166] (4) Put material c into the granulation chamber of a fluidized bed coater, heat 30 parts of glyceryl monostearate and 10 parts of carnauba wax to the molten state, spray them into the coater through a liquid spraying gun, coat material c, set the cooling temperature at 30 °C, and the coating time is 40 min. After cooling to room temperature, GABA sustained-release granules are obtained.

[0167] Example 17

[0168] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0169] (1) Take 25 parts of glyceryl monostearate and 15 parts of carnauba wax, heat them to the molten state, mix 120 parts of GABA evenly with the liquid to obtain material a, and keep it at 50 °C;

[0170] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a rocking granulator to size it to form solid granules, obtaining material b;

[0171] (3) Screen material b with a 40-mesh sieve to remove waste residue to obtain material c;

[0172] (4) Put material c into the granulation chamber of a fluidized bed coater, heat 20 parts of diglyceryl distearate and 20 parts of carnauba wax to the molten state, spray them into the coater through a liquid spraying gun, coat material c, set the cooling temperature at 30 °C, and the coating time is 40 min. After cooling to room temperature, GABA sustained-release granules are obtained.

[0173] Example 18

[0174] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0175] (1) Take 25 parts of glyceryl monostearate and 15 parts of carnauba wax, heat them to the molten state, mix 120 parts of GABA evenly with the liquid to obtain material a, and keep it at 50 °C;

[0176] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a swing granulator to size it to make solid granules, obtaining material b;

[0177] (3) Screen material b with a 40-mesh sieve to remove waste residue to obtain material c;

[0178] (4) Put material c into the granulation chamber of a fluidized bed coater, heat 20 parts of glyceryl behenate and 20 parts of carnauba wax to the molten state, spray them into the coater through a liquid spray gun, coat material c, set the cooling temperature at 30 °C, and the coating time at 40 min. After cooling to room temperature, GABA sustained-release granules are obtained.

[0179] Example 19

[0180] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0181] (1) Take 25 parts of glyceryl monostearate and 15 parts of carnauba wax, heat them to the molten state, mix 120 parts of GABA evenly with the liquid to obtain material a, and keep it at 50 °C;

[0182] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a swing granulator to size it to make solid granules, obtaining material b;

[0183] (3) Screen material b with a 40-mesh sieve to remove waste residue to obtain material c;

[0184] (4) Put material c into the granulation chamber of a fluidized bed coater, heat 20 parts of glyceryl monostearate and 20 parts of rice bran wax to the molten state, spray them into the coater through a liquid spray gun, coat material c, set the cooling temperature at 30 °C, and the coating time at 40 min. After cooling to room temperature, GABA sustained-release granules are obtained.

[0185] Example 20

[0186] This example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0187] (1) Take 25 parts of glyceryl monostearate and 15 parts of carnauba wax, heat them to the molten state, mix 120 parts of GABA evenly with the liquid to obtain material a, and keep it at 50 °C;

[0188] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a rocking granulator to perform sizing to make solid particles, obtaining material b;

[0189] (3) Use a 40-mesh sieve to screen out waste residue from material b to obtain material c;

[0190] (4) Put material c into the granulation chamber of a fluidized bed coater. Heat 20 parts of glycerol monostearate and 20 parts of candelilla wax to the molten state, spray them into the coater through a liquid spraying gun, perform coating on material c, set the cooling temperature to 30 °C, and the coating time to 40 min. After cooling to room temperature, obtain GABA sustained-release granules.

[0191] Example 21

[0192] This example provides a method for preparing GABA sustained-release granules, including the following steps:

[0193] (1) Take 25 parts of glycerol monostearate and 15 parts of carnauba wax, heat them to the molten state, mix 120 parts of GABA evenly with the liquid to obtain material a, and keep it at 50 °C;

[0194] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a rocking granulator to perform sizing to make solid particles, obtaining material b;

[0195] (3) Use a 40-mesh sieve to screen out waste residue from material b to obtain material c;

[0196] (4) Put material c into the granulation chamber of a fluidized bed coater. Heat 40 parts of glycerol monostearate to the molten state, spray it into the coater through a liquid spraying gun, perform coating on material c, set the cooling temperature to 30 °C, and the coating time to 40 min. After cooling to room temperature, obtain GABA sustained-release granules.

[0197] Example 22

[0198] This example provides a method for preparing GABA sustained-release granules, including the following steps:

[0199] (1) Take 25 parts of glycerol monostearate and 15 parts of carnauba wax, heat them to the molten state, mix 120 parts of GABA evenly with the liquid to obtain material a, and keep it at 50 °C;

[0200] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a rocking granulator to perform sizing to make solid particles, obtaining material b;

[0201] (3) Use a 40-mesh sieve to screen out waste residue from material b to obtain material c;

[0202] (4) Put material c into the granulation chamber of the fluidized coating machine. Heat 40 parts of carnauba wax to the molten state, spray it into the coating machine through a liquid spraying gun, coat material c, set the cooling temperature at 30 °C, and the coating time is 40 min. After cooling to room temperature, GABA sustained-release granules are obtained.

[0203] Comparative Example 1

[0204] This comparative example provides a method for preparing GABA sustained-release granules, which includes the following steps:

[0205] (1) Take 25 parts of glyceryl monostearate and 15 parts of carnauba wax, heat them to the molten state. After mixing 120 parts of GABA evenly with the liquid, obtain material a and keep it at 50 °C.

[0206] (2) Use a rotary granulator to extrude material a through a rotary knife from a sieve, cool it to room temperature, and then use a swing granulator for sizing to make solid granules, obtaining material b.

[0207] (3) Screen material b with a 40-mesh sieve to remove waste residue, obtaining material c.

[0208] (4) Put material c into the granulation chamber of the fluidized coating machine. Heat 20 parts of glyceryl monostearate and 20 parts of ethyl cellulose to the molten state, spray them into the coating machine through a liquid spraying gun, coat material c, set the cooling temperature at 30 °C, and the coating time is 40 min. After cooling to room temperature, GABA sustained-release granules are obtained.

[0209] The GABA sustained-release granule formulations of the above Examples 1 - 22 and Comparative Example 1 are shown in Table 1.

[0210] Table 1

[0211]

[0212] Experimental Example Evaluation and Test of Release Degree in Water

[0213] Weigh 2 g of the GABA sustained-release granule samples and GABA powder of the above examples and comparative examples respectively, place them in 200 ml of artificial simulated gastric juice (pH = 1.5, rich in dilute acid and pepsin), the rotation speed is 100 r·min, the water bath temperature is 37 °C. Take 1 mL of the medium solution at seven time points of 1 min, 1 h, 2 h, 2.5 h, 3 h, 3.5 h, and 4 h and supplement the same volume of the medium solution in time. Filter the taken medium solution through a hydrophilic filter membrane (0.22 μm), dilute the filtrate and perform derivatization treatment, and use high-performance liquid chromatography for detection and analysis. Calculate the release degree according to the change of GABA concentration data in the solution, with the completely released concentration of GABA in the sample being 100%. The calculation formula is as follows, and the results are shown in Table 2.

[0214] Release degree (%) = Concentration of GABA in solution / Concentration of completely released GABA * 100% 。

[0215] Table 2 Evaluation of GABA release degree

[0216] 1min 1h 2h 2.5h 3h 3.5h 4h Example 1 5％ 80％ 85％ 90％ 95％ 98％ 99％ Example 2 6％ 65％ 80％ 87％ 90％ 91％ 98％ Example 3 6％ 70％ 85％ 89％ 92％ 95％ 98％ Example 4 5％ 75％ 86％ 90％ 95％ 98％ 99％ Example 5 6％ 80％ 86％ 92％ 96％ 98％ 99％ Example 6 5％ 72％ 84％ 90％ 95％ 99％ 100％ Example 7 6％ 75％ 86％ 92％ 96％ 99％ 100％ Example 8 6％ 72％ 86％ 91％ 96％ 98％ 100％ Example 9 5％ 71％ 87％ 92％ 97％ 99％ 100％ Example 10 7％ 85％ 95％ 99％ 100％ 100％ 100％ Example 11 8％ 86％ 93％ 98％ 100％ 100％ 100％ Example 12 2％ 35％ 60％ 72％ 80％ 87％ 95％ Example 13 3％ 20％ 44％ 56％ 65％ 73％ 82％ Example 14 2％ 16％ 24％ 48％ 54％ 60％ 67％ Example 15 0％ 20％ 55％ 69％ 75％ 80％ 90％ Example 16 10％ 43％ 57％ 66％ 79％ 86％ 90％ Example 17 5％ 56％ 65％ 78％ 83％ 90％ 93％ Example 18 4％ 50％ 60％ 68％ 76％ 88％ 91％ Example 19 5％ 56％ 62％ 69％ 80％ 90％ 92％ Example 20 5％ 45％ 58％ 65％ 75％ 85％ 90％ Example 21 4％ 70％ 86％ 95％ 98％ 100％ 100％ Example 22 3％ 66％ 78％ 85％ 90％ 95％ 100％ Comparative Example 1 2％ 60％ 75％ 82％ 87％ 96％ 100％ GABA powder 100％ / / / / / /

[0217] As can be seen from the results in Table 2, the GABA powder was completely released after 1 minute. After it was prepared into sustained-release granules, its release effect could be significantly reduced. The release degree of GABA in Examples 1 - 9 reached over 90% at 3 h, while that in Examples 10 and 11 reached 100% at 3 h, indicating that the compound use of glyceride and plant wax as the matrix material had certain synergistic effects on the slow release of GABA.

[0218] In order to further improve the slow release effect of GABA, a coating material was used outside the intermediate granules. As can be seen from the release degree results of the GABA sustained-release granules in Examples 12 - 22 and Comparative Example 1, after using the coating material, the slow release effect of GABA could be improved. Further, the compound use of glyceride and plant wax as the coating material could significantly improve the slow release effect of GABA.

[0219] The above are only the embodiments of the present application and are not used to limit the present application. For those skilled in the art, various changes and modifications can be made to the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included within the scope of the claims of the present application.

Claims

1. A sustained-release granule containing γ-aminobutyric acid, characterized in that: The sustained-release particles include gamma-aminobutyric acid and a skeleton material, and the skeleton material includes at least glyceride and plant wax.

2. A sustained-release granule containing γ-aminobutyric acid, characterized in that: The sustained-release particles include a core material and a coating; the core material includes gamma-aminobutyric acid and a skeleton material, the skeleton material includes glyceride and / or plant wax; the coating includes glyceride and / or plant wax.

3. The sustained-release granules according to claim 2, characterized in that: The mass ratio of glyceride to vegetable wax in the coating is (0.1-3):1, preferably (0.5-2):

1.

4. The sustained-release granules according to claim 1 or 2, characterized in that: The mass ratio of glyceride to plant wax in the skeleton material is (0.1-3):

1.

5. The sustained-release granules according to claim 1 or 2, characterized in that: The glyceride includes one or more of glyceryl monostearate, glyceryl distearate, and glyceryl behenate; preferably, glyceryl monostearate; The vegetable wax includes one or more of carnauba wax, rice bran wax, and candelilla wax; preferably, carnauba wax.

6. The sustained-release granules according to claim 1 or 2, characterized in that: In terms of mass percentage, the γ-aminobutyric acid accounts for 40%-80% of the total mass of the sustained-release particles, preferably 50%-70%.

7. A method for preparing sustained-release granules, characterized in that: The method comprises at least the following steps: Step 1: Take glyceride and vegetable wax, heat them until they are melted, add γ-aminobutyric acid and mix them to form solid particles, thereby obtaining intermediate particles; Step 2: heating the glyceride and the vegetable wax until they are melted to obtain a coating material; Step 3: coating the intermediate particles with coating materials.

8. Use of the method according to claim 7 in improving the slow release effect of γ-aminobutyric acid.

9. Use of the sustained-release granules according to any one of claims 1 to 6 or the method according to claim 7 in the preparation of medicines, foods and / or cosmetics containing γ-aminobutyric acid.

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