Efficient sleep-aiding gamma-aminobutyric acid flash release tablet
By using erythritol as the drug-carrying skeleton to prepare γ-aminobutyric acid flash release tablets, the problem of holding urine in the prior art was solved, efficient sleep aiding and keeping the tablet dry, and improving sleep quality.
Patent Information
- Application Number
- CN202510857800.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-25
- Publication Date
- 2025-08-12
AI Technical Summary
Existing flash release tablets containing γ-aminobutyric acid can easily lead to increased urine volume in the sleep, causing a feeling of holding urine, and affecting the quality of sleep.
Erythritol is used as the drug-carrying framework to replace mannitol to prepare high-efficiency sleep aid γ-aminobutyric acid flash release tablets, and tablets are prepared through emulsification, degassing, injection molding, prefreezing, freeze-drying and other steps.
It avoids the feeling of holding urine, improves the sleep aid effect, ensures the continuity and comfort of sleep, and has low hygroscopicity of erythritol, keeping the tablet dry.
Smart Images
Figure CN120459046A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of health foods, and in particular relates to a high-efficiency sleep-inducing γ-aminobutyric acid flash-release tablet. Background Art
[0002] GABA, also known as 4-aminobutyric acid (GABA), is a compound with the chemical formula C₄H₄NO₂. It is an amino acid found widely in vertebrates, plants, and microorganisms. GABA is an important inhibitory neurotransmitter in the central nervous system, exhibiting good water solubility and thermal stability. As a small molecular weight, non-protein amino acid, GABA has been shown to be safe for consumption and can be used in the production of foods such as beverages. Studies have shown that consuming a certain amount of GABA can improve sleep quality and lower blood pressure, among other physiological benefits.
[0003] Flash-release tablets are rapidly disintegrating oral tablets that can be quickly decomposed in the mouth without the need for water and absorbed through the mucous membrane or gastrointestinal tract. Their core features are rapid onset of action and ease of administration, making them suitable for scenarios where swallowing is difficult or the drug needs to take effect quickly.
[0004] Currently, there are flash-release tablets containing γ-aminobutyric acid on the market, which are mainly used to improve the sleep effect of people with insomnia. However, most of these products use mannitol as a drug carrier skeleton. If taken before going to bed at night, they will have a certain diuretic effect, which can easily cause the user to feel the need to hold urine during sleep and easily wake up in the middle of the night, resulting in a poor sleep experience. Summary of the Invention
[0005] The purpose of the present invention is to provide a highly effective sleep-inducing γ-aminobutyric acid flash-release tablet, aiming to solve the technical problem that current flash-release tablets containing γ-aminobutyric acid easily cause the user to have increased urine volume during sleep, resulting in a feeling of holding urine.
[0006] To achieve the above objectives, the present invention provides a high-efficiency sleep-aiding γ-aminobutyric acid flash-release tablet comprising the following raw materials in percentage by weight: 3% to 5% γ-aminobutyric acid, 15% to 30% erythritol, 1% to 3% binder, and the balance water.
[0007] Optionally, the raw materials are included in the following mass percentages: 3.5% to 4.5% γ-aminobutyric acid, 20% to 25% erythritol, 1.5% to 2.5% binder, and the balance is water.
[0008] Optionally, the adhesive is a combination of pullulan and xanthan gum.
[0009] Optionally, the weight ratio of pullulan to xanthan gum in the adhesive is 1:(0.05~1).
[0010] The present invention also provides a method for preparing a highly effective sleep-inducing γ-aminobutyric acid flash-release tablet, which comprises the following steps: S10. Adding erythritol to the dissolved binder solution and mixing uniformly to obtain a first mixed solution; S20. Adding γ-aminobutyric acid to the first mixed solution and mixing uniformly to obtain a second mixed solution; S30. After emulsifying and degassing the second mixed solution, injection molding, pre-freezing, and freeze-drying are performed to obtain γ-aminobutyric acid flash-release tablets.
[0011] Optionally, in step S10, the adhesive solution is prepared by: dissolving xanthan gum in water; and then adding pullulan and mixing uniformly to obtain the adhesive solution.
[0012] Optionally, in step S30, the rotation speed of the emulsifier in the emulsifier is set to 6000-12000 rpm, the emulsification time is 8-20 minutes, and the degassing time is 5-15 minutes.
[0013] Optionally, in step S30, the pre-freezing temperature is -100 to -90°C, and the pre-freezing time is 8 to 15 minutes.
[0014] Optionally, in step S30, the freeze-drying comprises the following steps: S31, raise the temperature to -30°C in a freeze-drying chamber and freeze-dry for 1-2 hours; S32, raising the temperature to -25 to -10°C in a freeze-drying chamber and freeze-drying for 2.5 to 3.5 hours; S33. Raise the temperature to 25°C in a freeze-drying chamber and freeze-dry for 3.5-5 hours.
[0015] Optionally, in step S31, the freeze-drying product is first heated to -40°C and then placed in a freeze-drying box.
[0016] Optionally, in steps S31, S32, and S33, the heating rate is 1-1.5°C / min.
[0017] The present invention utilizes erythritol as the drug-carrying matrix, rather than the commonly used mannitol, to prevent the diuretic effect of mannitol, which can cause users to urinate. The flash-release tablets of this invention are less likely to wake users in the middle of the night, providing a more effective sleep aid. Furthermore, erythritol is less hygroscopic than mannitol, keeping the tablets dry after packaging. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying any creative work.
[0019] Figure 1 This is a schematic flow chart of an embodiment of a method for preparing a high-efficiency sleep-aiding γ-aminobutyric acid flash-release tablet provided by the present invention.
[0020] The purpose, features and advantages of the present invention will be further described with reference to the accompanying drawings and in conjunction with the embodiments. DETAILED DESCRIPTION
[0021] To make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them.
[0022] It should be noted that, in the embodiments, those without specifying specific conditions, are carried out according to conventional conditions or the conditions recommended by the manufacturer. Those for reagents or instruments used that do not specify the manufacturer are conventional products that can be purchased commercially. In addition, the meaning of "and / or" appearing in the full text includes three parallel schemes. Taking "A and / or B" as an example, it includes schemes A, B, or A and B that meet the same time. In addition, the technical solutions between the various embodiments can be combined with each other, but must be based on those of ordinary skill in the art. When the combination of the technical solutions is contradictory or cannot be realized, it should be considered that the combination of such technical solutions does not exist and is not within the scope of protection required by the present invention. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work belong to the scope of protection of the present invention.
[0023] The following combination Figure 1 A schematic flow chart of one embodiment of a method for preparing a high-efficiency sleep-inducing γ-aminobutyric acid (GABA) flash-release tablet is provided. The raw materials for preparing the GABA flash-release tablets in this embodiment are as follows: 3%-5% GABA, 15%-30% erythritol, 1%-3% binder, and the balance water. The binders are pullulan and xanthan gum, with a weight ratio of 1:(0.05-1).
[0024] The preparation method comprises the following steps: Step S10: Add erythritol to the dissolved adhesive solution and mix them evenly to obtain a first mixed solution.
[0025] In a specific implementation, the adhesive solution is prepared by dissolving xanthan gum in at least 1 times its weight of purified water, adding pullulan, and mixing uniformly to obtain the adhesive solution.
[0026] Step S20: Add γ-aminobutyric acid to the first mixed solution and mix them evenly to obtain a second mixed solution.
[0027] Step S30: After the second mixed solution is emulsified and degassed, injection molding, pre-freezing, and freeze-drying are performed to obtain γ-aminobutyric acid flash-release tablets.
[0028] In a specific implementation, the second mixed solution is poured into an emulsifier for emulsification, with the speed of the emulsifier set to 6000-12000 rpm, preferably 9000-10000 rpm. The emulsification time is 8-20 minutes, and the degassing time is 5-15 minutes.
[0029] When pre-freezing, first inject the emulsified liquid into the mold, then put it into a low-temperature refrigerator, set the temperature to -100~-90℃, and the pre-freezing time is 8~15 minutes.
[0030] The following steps are used for freeze drying: Step S31: heating the freeze-drying chamber to -30°C at a rate of 1-1.5°C / min and freeze-drying for 1-2 hours.
[0031] Step S32: heating the freeze-drying chamber to -25--10°C at a rate of 1-1.5°C / min, and freeze-drying for 2.5-3.5 hours.
[0032] Step S33: heating the freeze-drying chamber to 25°C at a rate of 1-1.5°C / min and freeze-drying for 3.5-5h.
[0033] In the technical solution of the present invention, by using erythritol as the drug-carrying matrix instead of the commonly used mannitol, the diuretic effect of mannitol can be avoided, which can cause users to feel the need to urinate. Taking the flash-release tablets of this solution can help users avoid waking up in the middle of the night, thus providing a more effective sleep aid. Furthermore, erythritol has lower hygroscopicity than mannitol, keeping the tablets dry after packaging.
[0034] The following further describes the process for preparing a high-efficiency sleep-inducing γ-aminobutyric acid flash-release tablet according to the present invention, but the embodiments of the present invention are not limited thereto. The experimental methods used in the following examples are all conventional methods unless otherwise specified. The manufacturer information of the drugs used is as follows: γ-aminobutyric acid was purchased from Huaxi Biotechnology Co., Ltd., erythritol was purchased from Baolingbao Biotechnology Co., Ltd., erythritol was purchased from Sanyuan Biotechnology Co., Ltd., and xanthan gum was purchased from Zhongxuan Biochemical Co., Ltd. Example 1
[0035] Prescription composition: 25.0g γ-aminobutyric acid 150g erythritol 8g pullulan 2g xanthan gum 500mL purified water Preparation process: 400 mL of purified water was measured and placed in a beaker, heated in a water bath at 50°C, the prescribed amount of pullulan and xanthan gum were weighed and placed in a beaker, the prescribed amount of erythritol was added and stirred and dissolved using a magnetic stirrer to obtain a first mixed solution; the prescribed amount of γ-aminobutyric acid was weighed and added to the first mixed solution, stirred until completely dissolved, and the remaining purified water was added to make the volume up to 500 mL to obtain a second mixed solution; the second mixed solution was emulsified in an emulsifier at a speed of 9000 rpm for 10 min; the emulsified liquid was vacuum degassed for 10 min to obtain an emulsion. The emulsion was dispensed into the blisters of an aluminum-plastic blister plate at a rate of 0.5 mL / tablet. The blister plate filled with the liquid was placed in a -95°C liquid nitrogen tunnel for pre-freezing for 12 min. The pre-frozen blister plate was transferred to a freeze dryer plate layer and the following freeze-drying curve was run: -40°C for 60 min; -30°C for 100 min; -25°C to -10°C for 180 min; and 25°C for 250 min. The blister plate was removed from the freeze dryer, film-wrapped and packaged in a sealing machine, and cut into pieces to obtain single 25 mg γ-aminobutyric acid flash-release tablets. Example 2
[0036] Prescription composition: 25.0g γ-aminobutyric acid 100g erythritol 8g pullulan 2g xanthan gum 500mL purified water Preparation process: 400 mL of purified water was measured and placed in a beaker, heated in a water bath at 50°C, the prescribed amount of pullulan and xanthan gum were weighed and placed in a beaker, the prescribed amount of erythritol was added and stirred and dissolved using a magnetic stirrer to obtain a first mixed solution; the prescribed amount of γ-aminobutyric acid was weighed and added to the first mixed solution, stirred until completely dissolved, and the remaining purified water was added to make the volume up to 500 mL to obtain a second mixed solution; the second mixed solution was emulsified in an emulsifier at a speed of 9000 rpm for 10 min; the emulsified liquid was vacuum degassed for 10 min to obtain an emulsion. The emulsion was dispensed into the blisters of an aluminum-plastic blister plate at a rate of 0.5 mL / tablet. The blister plate filled with the liquid was placed in a -95°C liquid nitrogen tunnel for pre-freezing for 12 min. The pre-frozen blister plate was transferred to a freeze dryer plate layer and the following freeze-drying curve was run: -40°C for 60 min; -30°C for 100 min; -25°C to -10°C for 180 min; and 25°C for 250 min. The blister plate was removed from the freeze dryer, film-wrapped and packaged in a sealing machine, and cut into pieces to obtain single 25 mg γ-aminobutyric acid flash-release tablets. Example 3
[0037] Prescription composition: 25.0g γ-aminobutyric acid 110g erythritol 8g pullulan 2g xanthan gum 500mL purified water Preparation process: 400 mL of purified water was measured and placed in a beaker, heated in a water bath at 50°C, the prescribed amount of pullulan and xanthan gum were weighed and placed in a beaker, the prescribed amount of erythritol was added and stirred and dissolved using a magnetic stirrer to obtain a first mixed solution; the prescribed amount of γ-aminobutyric acid was weighed and added to the first mixed solution, stirred until completely dissolved, and the remaining purified water was added to make the volume up to 500 mL to obtain a second mixed solution; the second mixed solution was emulsified in an emulsifier at a speed of 9000 rpm for 10 min; the emulsified liquid was vacuum degassed for 10 min to obtain an emulsion. The emulsion was dispensed into the blisters of an aluminum-plastic blister plate at a rate of 0.5 mL / tablet. The blister plate filled with the liquid was placed in a -95°C liquid nitrogen tunnel for pre-freezing for 12 min. The pre-frozen blister plate was transferred to a freeze dryer plate layer and the following freeze-drying curve was run: -40°C for 60 min; -30°C for 100 min; -25°C to -10°C for 180 min; and 25°C for 250 min. The blister plate was removed from the freeze dryer, film-wrapped and packaged in a sealing machine, and cut into pieces to obtain single 25 mg γ-aminobutyric acid flash-release tablets. Example 4
[0038] Prescription composition: 25.0g γ-aminobutyric acid 125g erythritol 8g pullulan 2g xanthan gum 500mL purified water Preparation process: 400 mL of purified water was measured and placed in a beaker, heated in a water bath at 50°C, the prescribed amount of pullulan and xanthan gum were weighed and placed in a beaker, the prescribed amount of erythritol was added and stirred and dissolved using a magnetic stirrer to obtain a first mixed solution; the prescribed amount of γ-aminobutyric acid was weighed and added to the first mixed solution, stirred until completely dissolved, and the remaining purified water was added to make the volume up to 500 mL to obtain a second mixed solution; the second mixed solution was emulsified in an emulsifier at a speed of 9000 rpm for 10 min; the emulsified liquid was vacuum degassed for 10 min to obtain an emulsion. The emulsion was dispensed into the blisters of an aluminum-plastic blister plate at a rate of 0.5 mL / tablet. The blister plate filled with the liquid was placed in a -95°C liquid nitrogen tunnel for pre-freezing for 12 min. The pre-frozen blister plate was transferred to a freeze dryer plate layer and the following freeze-drying curve was run: -40°C for 60 min; -30°C for 100 min; -25°C to -10°C for 180 min; and 25°C for 250 min. The blister plate was removed from the freeze dryer, film-wrapped and packaged in a sealing machine, and cut into pieces to obtain single 25 mg γ-aminobutyric acid flash-release tablets. Comparative Example 1
[0039] Prescription composition: 25.0g γ-aminobutyric acid 100g mannitol 8g pullulan 2g xanthan gum 500mL purified water Preparation process: 400 mL of purified water was measured and placed in a beaker, heated in a water bath at 50°C, the prescribed amount of pullulan and xanthan gum were weighed and placed in a beaker, the prescribed amount of mannitol was added and stirred and dissolved using a magnetic stirrer to obtain a first mixed solution; the prescribed amount of γ-aminobutyric acid was weighed and added to the first mixed solution, stirred until completely dissolved, and the remaining purified water was added to make the volume up to 500 mL to obtain a second mixed solution; the second mixed solution was emulsified in an emulsifier at a speed of 9000 rpm for 10 min; the emulsified liquid was vacuum degassed for 10 min to obtain an emulsion. The emulsion was dispensed into the blisters of an aluminum-plastic blister plate at a rate of 0.5 mL / tablet. The blister plate filled with the liquid was placed in a -95°C liquid nitrogen tunnel for pre-freezing for 12 min. The pre-frozen blister plate was transferred to a freeze dryer plate layer and the following freeze-drying curve was run: -40°C for 60 min; -30°C for 100 min; -25°C to -10°C for 180 min; and 25°C for 250 min. The blister plate was removed from the freeze dryer, film-wrapped and packaged in a sealing machine, and cut into pieces to obtain single 25 mg γ-aminobutyric acid flash-release tablets. Diuretic experiment
[0040] The blank control group and the rats of Examples 1-4 and Comparative Example 1 were gavaged with normal saline before the experiment, and the amount of normal saline was 5% of the body weight of the SD rats to increase the water burden of the rats. Subsequently, the experimental group was given a 50 mg / kg dose of flash-release tablets, and the five experimental groups were given the same amount of water. The SD rats were placed in metabolic cages for spontaneous diuresis. After the administration was completed, starting at 8 a.m. on the third day of administration, urine was collected from each rat in the time periods of 0-2 h, 2-4 h, and 4-8 h, and the urine volume was measured using a graduated cylinder, and the data was recorded. After the urine statistics were completed, data statistics and analysis were performed to analyze the diuretic properties of Examples 1-4 and Comparative Example 1.
[0041] The properties of each embodiment are compared in the following table: Table 1 Urine volume of rats in the blank control group, Examples 1-4 and Comparative Example 1 at 0-8h
[0042] Based on the above, the experimental data of the present invention, compared with the blank control group, showed that within 0-8 hours, the urine volume of mice administered with the flash-release tablets of Examples 1-4 was significantly reduced compared to the mice administered with the flash-release tablet of Comparative Example 1. This shows that the flash-release tablets containing erythritol do not increase urine volume in the user, are less likely to cause the user to hold urine during sleep, and do not wake up in the middle of the night. Therefore, the flash-release tablets of this solution have a more efficient and comfortable sleep-inducing effect. Stability test
[0043] The freeze-dried flash-release tablets containing γ-aminobutyric acid obtained in Example 1 and Comparative Example 1 were placed under 75% relative humidity (75% relative humidity at 25°C) for 10 days, and samples were taken on the 5th and 10th days, respectively, to measure the changes in weight gain after moisture absorption of the two flash-release tablets. The results are shown in Table 2.
[0044] Table 2 Test results of two freeze-dried flash-release tablets at 25°C and 75% relative humidity
[0045] As shown in Table 2, the hygroscopicity of the freeze-dried flash-release tablets containing γ-aminobutyric acid obtained in Example 1 and Comparative Example 1 increased with the increase in time under conditions of 25°C and 75% relative humidity. Under conditions of 25°C and 75% relative humidity, the flash-release tablets obtained in Example 1 had higher stability and their hygroscopicity increased slowly. In comparison, the flash-release tablets obtained in Comparative Example 1 had poorer stability and their hygroscopicity increased at a faster rate.
[0046] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.
[0047] The above-described embodiments merely represent several implementation methods of the present application. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that a person skilled in the art could make various modifications and improvements without departing from the spirit of the present application, all of which fall within the scope of protection of the present application. Therefore, the scope of protection of the present patent application shall be determined by the appended claims.
Claims
1. A highly effective sleep-inducing γ-aminobutyric acid flash-release tablet, characterized in that: The invention comprises the following raw materials in percentage by mass: 3% to 5% of gamma-aminobutyric acid, 15% to 30% of erythritol, 1% to 3% of a binder, and the balance being water.
2. The high-efficiency sleep-aiding γ-aminobutyric acid flash-release tablet according to claim 1, characterized in that: The invention comprises the following raw materials in percentage by mass: 3.5% to 4.5% of gamma-aminobutyric acid, 20% to 25% of erythritol, 1.5% to 2.5% of a binder, and the balance being water.
3. The high-efficiency sleep-aiding γ-aminobutyric acid flash-release tablet according to claim 1 or 2, characterized in that: The adhesive is a composition of pullulan and xanthan gum.
4. The high-efficiency sleep-aiding γ-aminobutyric acid flash-release tablet according to claim 3, characterized in that: The weight ratio of pullulan to xanthan gum in the adhesive is 1:(0.05-1).
5. A method for preparing the high-efficiency sleep-aiding γ-aminobutyric acid flash-release tablets according to claim 1, characterized in that: The steps include: S10. Adding erythritol to the dissolved binder solution and mixing uniformly to obtain a first mixed solution; S20. Adding γ-aminobutyric acid to the first mixed solution and mixing uniformly to obtain a second mixed solution; S30. After emulsifying and degassing the second mixed solution, injection molding, pre-freezing, and freeze-drying are performed to obtain γ-aminobutyric acid flash-release tablets.
6. The method for preparing the high-efficiency sleep-aiding γ-aminobutyric acid flash-release tablets according to claim 5, characterized in that: In step S10, the adhesive solution is prepared by dissolving xanthan gum in water; and then adding pullulan and mixing the mixture uniformly to obtain the adhesive solution.
7. The method for preparing the high-efficiency sleep-aiding γ-aminobutyric acid flash-release tablets according to claim 5, characterized in that: In the step S30, the rotation speed of the emulsifier is set to 6000-12000 rpm, the emulsification time is 8-20 minutes, and the degassing time is 5-15 minutes.
8. The method for preparing the high-efficiency sleep-aiding γ-aminobutyric acid flash-release tablets according to claim 5, wherein: In step S30, the pre-freezing temperature is -100 to -90°C, and the pre-freezing time is 8 to 15 minutes.
9. The method for preparing the high-efficiency sleep-aiding γ-aminobutyric acid flash-release tablets according to claim 5, wherein: In step S30, the freeze-drying comprises the following steps: S31, raising the temperature to -30°C in a freeze drying chamber and freeze drying for 1-2 hours; S32, raising the temperature of the freeze-dried product to -25 to -10°C in a freeze-drying chamber and freeze-drying for 2.5 to 3.5 hours; S33. Raise the temperature to 25°C in a freeze drying chamber and freeze-dry for 3.5-5 hours.
10. The method for preparing the high-efficiency sleep-aiding γ-aminobutyric acid flash-release tablets according to claim 9, wherein: In steps S31, S32, and S33, the heating rate is 1-1.5°C / min.