阅读说明：本技术 百蕊颗粒制剂及其制备方法 (Granular preparation of bastardtoad herb and its preparation method ) 是由 管悦琴 罗雪峰 李铁程 于 2021-02-08 设计创作，主要内容包括：本申请供了一种百蕊颗粒制剂的制备方法,该制备方法对传统颗粒制剂的制备方法进行改革,将百蕊草提取物溶液与粘结剂、润滑剂进行混合后采用干燥处理的制备方法进行造粒,同时经过两次过筛处理,得到性质优异的百蕊颗粒制剂。喷雾干燥的制备工艺过程简单、干燥温和,所得颗粒粒径分布窄,同时所制得的百蕊颗粒制剂固体分散体中活性成分主要以无定形形式均匀分散,具有较高的吉布斯能,故而在溶解时所需能量较少,能够极大提高了百蕊颗粒制剂总黄酮等活性成分的溶解性,提高了使用效果,扩大了百蕊颗粒制剂的应用广泛性。(The application provides a preparation method of a thesium Chinese granular preparation, which reforms the preparation method of the traditional granular preparation, and the thesium Chinese extract solution, a binder and a lubricant are mixed and then granulated by adopting a preparation method of drying treatment, and meanwhile, the thesium Chinese granular preparation with excellent properties is obtained by twice sieving treatment. The preparation process of spray drying is simple, the drying is mild, the particle size distribution of the obtained particles is narrow, and meanwhile, the active ingredients in the solid dispersion of the prepared thesium chinense particle preparation are uniformly dispersed mainly in an amorphous form and have higher Gibbs energy, so that the energy required for dissolving is less, the solubility of the active ingredients such as total flavonoids of the thesium chinense particle preparation can be greatly improved, the use effect is improved, and the application range of the thesium chinense particle preparation is expanded.)

1. A preparation method of a thesium particle preparation is characterized by comprising the following steps:

providing the components of the thesium Chinese particle preparation, wherein the thesium Chinese particle preparation comprises thesium Chinese extract, a binder, a filler and a lubricant;

drying the thesium Chinese extract, and dissolving in an organic solvent to obtain thesium Chinese extract solution;

mixing the thesium Chinese extract solution with the binder and the lubricant to obtain a first mixed solution;

drying the first mixed solution, and performing first sieving treatment to obtain first granules;

and mixing the first granules with the filler, performing second sieving treatment, and drying to obtain the thesium granule preparation.

2. The method for preparing a thesium particle preparation according to claim 1, wherein in the step of subjecting the first mixed solution to drying treatment, the drying treatment is performed by spray drying, and conditions of the spray drying are set as follows:

the inlet temperature is set to be 165-170 ℃, the outlet temperature is set to be 98-102 ℃, the flow rate of the first mixed liquid is set to be 10-14L/h, and the solid content of the first mixed liquid is set to be 5-6%.

3. The process for preparing granular thesium chinense preparation as claimed in claim 1, wherein in the first sieving step, the number of the first sieving is 60-70 mesh; and/or the presence of a gas in the gas,

in the second sieving step, the number of the second sieving meshes is 20-24 meshes.

4. A thesium particle preparation is characterized by comprising the following components in parts by weight:

5. the particle formulation of thesium chinense pursh of claim 4 wherein the thesium chinense pursh extract comprises a mixture of thesium chinense pursh total flavone extract, thesium chinense pursh polysaccharide extract, and thesium chinense alkaloid extract.

6. The thesium particle preparation as claimed in claim 4, wherein the thesium total flavone extract is contained in an amount of 0.1-1% by mass.

7. The thesine particle formulation of claim 6, wherein the thesine total flavone extract includes at least one of thesine I, thesine II, and thesine III.

8. A particle formulation according to any of claims 4 to 7, wherein the binder is at least one selected from polyvinylpyrrolidone and hydroxypropylmethylcellulose.

9. A particle formulation according to any of claims 4 to 7, wherein the filler is at least one selected from lactose, pregelatinized starch, microcrystalline cellulose.

10. The particle formulation of thesium barbarum of claims 4-7 wherein the lubricant is at least one selected from the group consisting of colloidal silicon dioxide and magnesium stearate.

Technical Field

The application belongs to the technical field of traditional Chinese medicine granules, and particularly relates to a thesium granule preparation and a preparation method thereof.

Background

Thesium chinense is the whole plant of Thesium chinense Turcaz of Santalaceae, and is distributed in north and south provinces of China. Thesium was originally recorded in the materia Medica of the book Jing of the drawing, has slightly astringent and bitter taste and warm nature, is often called plant antibiotic and is a common traditional Chinese medicine in China. Has good antibacterial effect, and has effects in invigorating qi, invigorating kidney, clearing away heat and toxic materials. Can be used for treating lumbago due to kidney deficiency, dizziness, acute mastitis, acute tonsillitis, pharyngitis, pneumonia, lung abscess, upper respiratory infection, lobar pneumonia, and various infections.

The thesium Chinese contains various compounds such as flavone, polysaccharide, alkaloid, organic acid and the like, and the flavonoid compound is most abundant. Generally, the thesium Chinese preparation is prepared by adding dextrin and powdered sugar, and flavone in the thesium Chinese granule preparation prepared by the traditional method has low solubility and low bioavailability, and is not beneficial to improving the action effect in use.

Disclosure of Invention

The application aims to provide a thesium particle preparation and a preparation method thereof, and aims to solve the problem of low flavone solubility of the thesium preparation in the prior art.

In order to achieve the purpose of the application, the technical scheme adopted by the application is as follows:

in a first aspect, the present application provides a method for preparing a thesium particle formulation, comprising the steps of:

providing the components of the thesium Chinese particle preparation, wherein the thesium Chinese particle preparation comprises thesium Chinese extract, a binder, a filler and a lubricant;

drying the thesium Chinese extract, and dissolving in an organic solvent to obtain thesium Chinese extract solution;

mixing the thesium Chinese extract solution with the binder and the lubricant to obtain a first mixed solution;

drying the first mixed solution, and performing first sieving treatment to obtain first granules;

and mixing the first granules with the filler, performing second sieving treatment, and drying to obtain the thesium granule preparation.

In a second aspect, the present application provides a thesium granule preparation, which comprises the following components in parts:

according to the preparation method of the thesium chinense particle preparation, provided by the first aspect of the application, the preparation method is an improvement of the traditional preparation method of particle preparations, and the thesium chinense extract solution, the binder and the lubricant are mixed and then granulated by adopting a preparation method of drying treatment, and meanwhile, the thesium chinense particle preparation with excellent properties is obtained through twice screening treatment. The preparation process of spray drying is simple, the drying is mild, the particle size distribution of the obtained particles is narrow, and meanwhile, the active ingredients in the solid dispersion of the prepared thesium chinense particle preparation are uniformly dispersed mainly in an amorphous form and have higher Gibbs energy, so that the energy required for dissolving is less, the solubility of the active ingredients such as total flavonoids of the thesium chinense particle preparation can be greatly improved, the use effect is improved, and the application range of the thesium chinense particle preparation is expanded.

The thesium particle preparation that this application second aspect provided, this thesium particle preparation has included thesium extract and binder, filler and lubricant, wherein, this thesium particle preparation has provided binder, filler and lubricant and has carried out the complex formulation with thesium extract and use, owing to provide the lubricant, be favorable to granule smooth preparation in spray drying's preparation process, and the binder can be favorable to thesium extract and each auxiliary material auxiliary agent to mix, the filler then is favorable to improving thesium particle preparation's plumpness, guarantee thesium particle preparation size even, active ingredient can evenly disperse, be favorable to improving active ingredient's solubility, improve the result of use.

Detailed Description

In order to make the technical problems, technical solutions and advantageous effects to be solved by the present application more clearly apparent, the present application is further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present application and are not intended to limit the present application.

In this application, the term "and/or" describes an association relationship of associated objects, meaning that there may be three relationships, e.g., a and/or B, which may mean: a is present alone, A and B are present simultaneously, and B is present alone. Wherein A and B can be singular or plural. The character "/" generally indicates that the former and latter associated objects are in an "or" relationship.

In the present application, "at least one" means one or more, "a plurality" means two or more. "at least one of the following" or similar expressions refer to any combination of these items, including any combination of the singular or plural items. For example, "at least one (a), b, or c", or "at least one (a), b, and c", may each represent: a, b, c, a-b (i.e., a and b), a-c, b-c, or a-b-c, wherein a, b, and c may be single or plural, respectively.

It should be understood that, in various embodiments of the present application, the sequence numbers of the above-mentioned processes do not mean the execution sequence, some or all of the steps may be executed in parallel or executed sequentially, and the execution sequence of each process should be determined by its function and inherent logic, and should not constitute any limitation to the implementation process of the embodiments of the present application.

The terminology used in the embodiments of the present application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in the examples of this application and the appended claims, the singular forms "a", "an", and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.

The weight of the related components mentioned in the description of the embodiments of the present application may not only refer to the specific content of each component, but also represent the proportional relationship of the weight among the components, and therefore, the content of the related components is scaled up or down within the scope disclosed in the description of the embodiments of the present application as long as it is scaled up or down according to the description of the embodiments of the present application. Specifically, the mass described in the specification of the embodiments of the present application may be a mass unit known in the chemical industry field such as μ g, mg, g, kg, etc.

The terms "first" and "second" are used for descriptive purposes only and are used for distinguishing purposes such as substances from one another, and are not to be construed as indicating or implying relative importance or implying any number of technical features indicated. For example, a first XX may also be referred to as a second XX, and similarly, a second XX may also be referred to as a first XX, without departing from the scope of embodiments of the present application. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature.

In a first aspect, embodiments of the present application provide a method for preparing a thesium particle formulation, comprising the steps of:

s01, providing components of a thesium Chinese particle preparation, wherein the thesium Chinese particle preparation comprises a thesium Chinese extract, a binder, a filler and a lubricant;

s02, drying the thesium chinense extract, and dissolving the thesium chinense extract in an organic solvent to obtain thesium chinense extract solution;

s03, mixing the thesium chinense extract solution with a binder and a lubricant to obtain a first mixed solution;

s04, drying the first mixed solution, and performing first sieving treatment to obtain first particles;

and S05, mixing the first granules with a filling agent, performing second sieving treatment, and drying to obtain the thesium granule preparation.

According to the preparation method of the thesium chinense particle preparation, provided by the first aspect of the application, the preparation method is an improvement of the traditional preparation method of particle preparations, and the thesium chinense extract solution, the binder and the lubricant are mixed and then granulated by adopting a preparation method of drying treatment, and meanwhile, the thesium chinense particle preparation with excellent properties is obtained through twice screening treatment. The preparation process of spray drying is simple, the drying is mild, the particle size distribution of the obtained particles is narrow, and meanwhile, the active ingredients in the solid dispersion of the prepared thesium chinense particle preparation are uniformly dispersed mainly in an amorphous form and have higher Gibbs energy, so that the energy required for dissolving is less, the solubility of the active ingredients such as total flavonoids of the thesium chinense particle preparation can be greatly improved, the use effect is improved, and the application range of the thesium chinense particle preparation is expanded.

In step S01, components of a thesium particle formulation are provided, wherein the thesium particle formulation includes thesium chinense extract, a binder, a filler, and a lubricant.

In another aspect, the present embodiment provides a thesium particle preparation, which includes the following components in parts:

the thesium particle preparation comprises a thesium extract, a binder, a filler and a lubricant, wherein the thesium extract is compounded with the binder, the filler and the lubricant, the lubricant is beneficial to smooth preparation of particles in a spray drying preparation process, the binder can be beneficial to mixing of the thesium extract and auxiliary materials, the filler is beneficial to improving the fullness of the thesium particle preparation, the size uniformity of the thesium particle preparation is ensured, active ingredients can be uniformly dispersed, the improvement of the solubility of the active ingredients is facilitated, and the use effect is improved.

Specifically, the thesium Chinese particle preparation comprises 20-30 parts of thesium Chinese extract, 20-30 parts of thesium Chinese extract are provided, the active component content of thesium Chinese in the obtained thesium Chinese particle preparation is high, and the effect of the particle preparation is favorably exerted. In the specific embodiment, the added parts of the thesium Chinese extract are selected from 20 parts, 21 parts, 22 parts, 23 parts, 24 parts, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts and 30 parts.

In some embodiments, the method of extracting the thesium chinense extract comprises the steps of:

G01. providing herba Thesii whole plant, soaking/decocting to obtain herba Thesii decoction;

G02. concentrating the herba Thesii decoction to obtain herba Thesii concentrated solution with relative density of 1.25-1.35;

G03. carrying out alcohol extraction treatment on the thesium Chinese concentrated solution to obtain an alcohol extract;

G04. concentrating the supernatant under reduced pressure to obtain herba Thesii extract.

In step G01, the method further comprises, before the soaking/decocting step: drying the whole thesium chinense, wherein the drying temperature is 60-80 ℃.

The step of soaking/decocting the whole plant of thesium Chinese includes: adding water with the weight 10-14 times of the total weight of the thesium Chinese into the mixture, soaking the mixture for 1-2 hours, and then decocting the mixture for the first time, wherein the decocting time is 110-130 minutes; adding water which is 8-12 times of the total weight of the thesium Chinese into the mixture, and then carrying out secondary decoction for 50-70 min; wherein the decocting temperature is 98-100 deg.C. Through twice soaking/decocting treatment, various active extracts such as flavone, polysaccharide, alkaloid and the like in the whole plant of the thesium Chinese can be extracted.

In the step G03, in the step of performing alcohol extraction treatment on the thesium Chinese herb concentrated solution, the alcohol extraction treatment method comprises the following steps: firstly extracting with 70-75% ethanol in an amount which is 2 times the volume of the extract, then extracting with 90-95% ethanol in an equal volume percentage, and combining the extracting solutions to obtain an ethanol extracting solution.

Furthermore, the thesium Chinese extract comprises a mixture of thesium Chinese total flavone extract, thesium Chinese polysaccharide extract and thesium Chinese alkaloid extract, and the extraction method can ensure that the thesium Chinese total flavone extract, the thesium Chinese polysaccharide extract and the thesium Chinese alkaloid extract are extracted to the maximum extent, so that the content of active components is improved.

Furthermore, the mass percentage of the thesium Chinese total flavone extract is 0.1-1%, the mass percentage of the thesium Chinese total flavone extract is controlled to be moderate, active ingredients can be uniformly dispersed in the thesium Chinese particle preparation obtained after spray drying treatment, the improvement of the solubility of the active ingredients, particularly the total flavone extract, is facilitated, and the use effect is improved. In the specific embodiment of the invention, the mass percentage of the total flavonoids of thesium Chinese is 1%.

Further, the herba Thesii total flavone extract comprises at least one of herba Thesii extract I, herba Thesii extract II, and herba Thesii extract III. Wherein, the thesine I is 3, 5, 7, 4: tetrahydroxyflavone-3-glucose rhamnoside, which is yellow needle crystal structure; thesine II is 3, 5, 7, 4: tetrahydroxyflavone-3-glucoside, which is in a yellow needle crystal structure; the thesine III is kaempferol, and is yellow sand grain crystal. The thesium Chinese medicine granule preparation has powerful functions of resisting bacteria, resisting virus, resisting tumor, resisting inflammation, relieving pain, etc. and may be used widely.

The thesium Chinese particle preparation comprises 70-80 parts of a binder, and the binder is added to facilitate uniform mixing of thesium Chinese extract and various auxiliary materials, so that the auxiliary materials wrap the thesium Chinese extract, preparation of the thesium Chinese particle preparation is facilitated, and uniform dispersion of active substances of the thesium Chinese is facilitated. In a particular embodiment of the invention, the binder is selected from 70 parts, 71 parts, 72 parts, 73 parts, 74 parts, 75 parts, 76 parts, 77 parts, 78 parts, 79 parts, 80 parts.

Further, the binder is at least one selected from polyvinylpyrrolidone and hydroxypropyl methylcellulose.

Specifically, the thesium Chinese medicine granule preparation comprises 50-60 parts of a filler, the filler is added, the thesium Chinese medicine granule preparation is favorably formed in the spray drying process, and meanwhile, the thesium Chinese medicine granule preparation plays a supporting role, is favorable for granulation, and is formed into granules with uniform sizes. In a particular embodiment of the invention, the filler is selected from 50 parts, 51 parts, 52 parts, 53 parts, 54 parts, 55 parts, 56 parts, 57 parts, 58 parts, 59 parts, 60 parts.

Further, the filler is at least one selected from lactose, pregelatinized starch, and microcrystalline cellulose.

Specifically, the thesium particle preparation comprises 5-10 parts of lubricant, the lubricant is added, smooth preparation of the particle in a spray drying preparation process is facilitated, the smoothing effect is improved, active ingredients are uniformly dispersed, and the solubility of the prepared thesium particle preparation is improved. In the embodiment of the present invention, the added parts of the lubricant are selected from 5 parts, 6 parts, 7 parts, 8 parts, 9 parts and 10 parts.

Further, the lubricant is selected from at least one of colloidal silicon dioxide and magnesium stearate.

In step S02, the thesium chinense extract is dried and then dissolved in an organic solvent to obtain a thesium chinense extract solution. The water content of the extract of the thesium Chinese is less than or equal to 13 percent, which is not beneficial to directly preparing the granules, so the extract needs to be dried.

Further, in the step of drying the thesium Chinese extract, the thesium Chinese extract is dried for 5-6 hours at 80-90 ℃ to obtain the thesium Chinese extract with the water content less than or equal to 5%, and subsequent tests are facilitated.

Further, an organic solvent is provided, including, but not limited to, anhydrous ethanol. Providing absolute ethyl alcohol, and dissolving the dried thesium Chinese extract into the absolute ethyl alcohol to obtain thesium Chinese extract solution. Wherein the mass ratio of the thesium Chinese extract to the organic solvent is 1: 8-10.

In step S03, the thesium chinense extract solution is mixed with the binder and the lubricant to obtain a first mixed solution. Wherein, the thesium Chinese extract solution, the binder and the lubricant are mixed for 20-30 minutes under the condition of 600-800 rpm, so that the thesium Chinese extract solution, the binder and the lubricant are uniformly mixed, and granulation is facilitated.

In step S04, the first mixed solution is dried and subjected to a first sieving process to obtain first granules. The preparation method is an improvement on the traditional preparation method of the particle preparation, the thesium Chinese extract solution, the binder and the lubricant are mixed and then granulated by adopting a spray drying preparation method, the preparation process of drying treatment is simple, drying is mild, the particle size distribution of the obtained particles is narrow, and meanwhile, the active ingredients in the prepared thesium Chinese particle preparation solid dispersion are uniformly dispersed mainly in an amorphous form and have higher Gibbs energy, so that the energy required for dissolving is less, the solubility of the active ingredients such as total flavonoids of the thesium Chinese particle preparation can be greatly improved, the use effect is improved, and the application universality of the thesium Chinese particle preparation is enlarged.

Further, in the step of drying the first mixed solution, the drying treatment is performed by spray drying, and the conditions of the spray drying are set as follows:

the inlet temperature is set to be 165-170 ℃, the outlet temperature is set to be 98-102 ℃, the flow rate of the first mixed liquid is set to be 10-14L/h, and the solid content of the first mixed liquid is set to be 5-6%.

Based on the set inlet temperature of 165-170 ℃ and the set outlet temperature of 98-102 ℃, the obtained thesium Chinese particle preparation is fine and smooth, high in uniformity and high in solubility by controlling the inlet temperature and the outlet temperature, and the solubility of active ingredients is favorably ensured. If the inlet temperature and the outlet temperature are too low or too high, the thesium particle preparation is rough and uneven, the particle uniformity is poor, the components are not uniformly dispersed, and the dissolution is not facilitated. In a specific embodiment of the invention, the inlet temperature is set at 168 ℃ and the outlet temperature is set at 100 ℃.

The flow rate of the first mixed solution is set to be 10-14L/h, the flow rate of the first mixed solution is controlled to be moderate, active ingredients in the solid dispersion of the thesium particle preparation are uniformly dispersed mainly in an amorphous form, Gibbs energy is improved, energy required by the obtained formed particles is less when the particles are dissolved, the solubility of the active ingredients such as total flavonoids of the thesium particle preparation can be greatly improved, and the using effect is improved. If the flow rate of the first mixed solution is too slow, the production rate is influenced, and the uniform dispersion condition of the active ingredients is also influenced; if the flow velocity is too high, the molding of the product is not facilitated, and the uniformity of the particles is affected. In the embodiment of the invention, the flow rate of the first mixed liquid is set to be 12L/h.

Setting the solid content of the first mixed solution to be 5-6%, controlling the solid content of the first mixed solution to be beneficial to controlling the discharging speed, and if the solid content is too low, the water content is too high to influence the subsequent drying time and influence the particle forming; if the solid content is too high, the discharging speed is too fast, the uniformity is poor, and the solubility is influenced. In an embodiment of the present invention, the solids content of the first mixed liquor is set to 5.5%.

Further, the first sieving treatment was performed to obtain first granules. In the first sieving step, the sieving mesh number of the first sieving is 60-70 meshes, and the first sieving is performed to sieve out particles with overlarge particle sizes.

In step S05, the first granules and the filler are mixed, sieved and dried to obtain the thesium granule.

Wherein, the first particles and the filler are mixed for 20 to 30 minutes under the condition of 50 to 60rpm, so as to ensure that the first particles and the filler are uniformly mixed and the effect is better.

Further, in the second sieving step, the number of the second sieving meshes is 20-24 meshes. The particle size of the obtained thesium particle preparation is ensured to be 20-24 meshes, the particle is uniform, and the improvement of the dissolubility can be ensured.

Further, the drying treatment is carried out for 100-120 minutes at 65 ℃, so that the obtained thesium particle preparation is dry and uniform in size and is suitable for storage and use.

The following description will be given with reference to specific examples.

Example 1

Granular preparation of bastardtoad herb and its preparation method

Granular preparation of bastardtoad

The thesium particle preparation comprises the following components in parts by weight:

wherein the herba Thesii extract comprises mixture of herba Thesii total flavone extract, herba Thesii polysaccharide extract, and herba Thesii alkaloid extract; and the mass percentage content of the thesium Chinese total flavone extract is 1 percent; the herba Thesii total flavone extract comprises at least one of herba Thesii extract I, herba Thesii extract II, and herba Thesii extract III; the binder is selected from polyvinylpyrrolidone, the filler is selected from lactose, and the lubricant is selected from colloidal silicon dioxide.

Preparation method of thesium granule preparation

Providing the components of the thesium particle formulation provided in example 1;

drying herba Thesii extract at 80 deg.C for 5 hr, dissolving in anhydrous ethanol to obtain herba Thesii extract solution;

mixing the thesium Chinese extract solution with a binder and a lubricant for 20 minutes at 600rpm to obtain a first mixed solution;

spray drying the first mixed solution, and performing first sieving treatment to obtain first granules; wherein the conditions for spray drying are set as follows: setting the inlet temperature to 165 ℃, the outlet temperature to 98 ℃, the flow rate of the first mixed liquid to 10L/h and the solid content of the first mixed liquid to 5%; the number of the meshes of the first screening treatment is 60 meshes;

mixing the first granules and the filler at 600rpm for 20 min, sieving for 20 meshes, and drying at 65 deg.C for 100-120 min to obtain herba Thesii granule.

Example 2

Granular preparation of bastardtoad herb and its preparation method

Granular preparation of bastardtoad

The thesium particle preparation comprises the following components in parts by weight:

wherein the herba Thesii extract comprises mixture of herba Thesii total flavone extract, herba Thesii polysaccharide extract, and herba Thesii alkaloid extract; and the mass percentage content of the thesium Chinese total flavone extract is 0.8 percent; the herba Thesii total flavone extract comprises at least one of herba Thesii extract I, herba Thesii extract II, and herba Thesii extract III; the binder is selected from polyvinylpyrrolidone, the filler is selected from lactose, and the lubricant is selected from colloidal silicon dioxide.

Preparation method of thesium granule preparation

Providing the components of the thesium particle formulation provided in example 2;

drying herba Thesii extract at 85 deg.C for 5.5 hr, dissolving in anhydrous ethanol to obtain herba Thesii extract solution;

mixing the thesium Chinese extract solution with a binder and a lubricant for 25 minutes at 650rpm to obtain a first mixed solution;

spray drying the first mixed solution, and performing first sieving treatment to obtain first granules; wherein the conditions for spray drying are set as follows: setting the inlet temperature to be 168 ℃, the outlet temperature to be 100 ℃, the flow rate of the first mixed liquid to be 12L/h and the solid content of the first mixed liquid to be 5.5 percent; the number of the meshes of the first screening treatment is 65 meshes;

mixing the first granules and the filler at 600rpm for 20 minutes, performing a second sieving treatment at 22 meshes, and performing a drying treatment at 65 ℃ for 100-120 minutes to obtain the thesium particle preparation.

Example 3

Granular preparation of bastardtoad herb and its preparation method

Granular preparation of bastardtoad

The thesium particle preparation comprises the following components in parts by weight:

wherein the herba Thesii extract comprises mixture of herba Thesii total flavone extract, herba Thesii polysaccharide extract, and herba Thesii alkaloid extract; and the mass percentage content of the thesium Chinese total flavone extract is 0.8 percent; the herba Thesii total flavone extract comprises at least one of herba Thesii extract I, herba Thesii extract II, and herba Thesii extract III; the binder is selected from hydroxypropyl methylcellulose, the filler is selected from pregelatinized starch, and the lubricant is selected from colloidal silicon dioxide.

Preparation method of thesium granule preparation

Providing the components of the thesium particle formulation provided in example 3;

drying herba Thesii extract at 85 deg.C for 5.8 hr, dissolving in anhydrous ethanol to obtain herba Thesii extract solution;

mixing the thesium Chinese extract solution with a binder and a lubricant for 30 minutes at 650rpm to obtain a first mixed solution;

spray drying the first mixed solution, and performing first sieving treatment to obtain first granules; wherein the conditions for spray drying are set as follows: setting the inlet temperature to be 170 ℃, the outlet temperature to be 102 ℃, the flow rate of the first mixed solution to be 14L/h, and the solid content of the first mixed solution to be 6%; the number of the meshes of the first screening treatment is 70 meshes;

mixing the first granules and the filler at 600rpm for 20 minutes, performing a second sieving treatment at 22 meshes, and performing a drying treatment at 65 ℃ for 100-120 minutes to obtain the thesium particle preparation.

And (3) testing properties:

physicochemical property tests were performed on the thesium particle preparations prepared in examples 1-3, wherein the test items in the quality standards include properties, identification, moisture, particle size, and content, all referring to the national food and drug administration standard YBZ 10642009.

1. The characteristics are as follows:

the color, smell, etc. of the product were observed.

2. And (3) identification:

the method comprises the following steps: taking the thesium particle preparation prepared in the embodiment 1-3 as a test solution and a reference solution respectively, taking 0.3g of thesium chinense reference medicinal material, putting into a triangular flask with a plug, adding 25ml of methanol, carrying out ultrasonic treatment for 30min, filtering, washing filter residues with a small amount of methanol, combining the filtrate and the washing solution, evaporating to dryness, and adding 30ml of methanol to the residues for dissolving. Adding 25% hydrochloric acid 5ml, refluxing in water bath for 1 hr, and cooling to obtain control solution. Sucking 10 μ l of the above three solutions, respectively dropping on the same silica gel G thin layer plate with sodium carboxymethylcellulose as binder, developing with toluene-ethyl formate-formic acid (5:4:1) as developing agent, taking out, air drying, spraying aluminum dichloride test solution, air drying, inspecting under ultraviolet lamp (365nm), and displaying fluorescent spots of the same color in the chromatogram of the test solution at the positions corresponding to those of the control solution and the control solution.

3. Granularity:

the method comprises the following steps: the four parts of Chinese pharmacopoeia 2020 edition particle size and particle size distribution determination method.

4. Flavonoid active ingredient in herba Thesii granule

The method comprises the following steps: measuring by high performance liquid chromatography (four parts of China pharmacopoeia 2020 edition). Chromatographic conditions and system adaptability tests are carried out by taking octadecylsilane chemically bonded silica as a filler; methanol-0.5% phosphoric acid solution (62:38) is used as a mobile phase; the detection wavelength is 368 nm; column temperature: 30 ℃; flow rate: 1.0 ml/min. The theoretical plate number is not lower than 4000 calculated according to the peak of kaempferol.

Preparation of control solutions: taking a proper amount of kaempferol reference substance which is subjected to phosphorus pentoxide reduced pressure drying for 48h, precisely weighing, adding methanol to prepare a solution containing 40 mu g of kaempferol per 1ml, and shaking up to obtain the kaempferol.

Preparation of a test solution: taking the product with different loading amounts, grinding, taking 1g, precisely weighing, adding 10ml of distilled water, heating to dissolve, cooling, slowly adding 80ml of ethanol, standing for 30min, filtering, washing residues with a small amount of 85% ethanol twice, mixing the filtrate and a washing solution, evaporating to dryness, adding 40ml of water to the residues to dissolve, adding the obtained solution onto a treated polyamide column (30-60 meshes, 7g, the inner diameter of the column is 2cm, loading the column by a wet method), controlling the flow rate for 1 drop/3-4 s, eluting with 100ml of water, discarding the water washing solution, eluting with 200ml of 60% ethanol, collecting the ethanol eluate, concentrating under reduced pressure to dryness, adding 30ml of methanol to dissolve the residues, adding 5ml of 25% hydrochloric acid into a water bath, refluxing for 1h, cooling, adding methanol to fix the volume to 50ml, shaking, filtering, and taking the subsequent filtrate to obtain the product.

The determination method comprises the following steps: precisely sucking 10 μ l of each of the reference solution and the sample solution, injecting into liquid chromatograph, and measuring.

The content of herba Thesii in each bag is not less than 7.0mg, calculated by kaempferol (C15H10O 6). [ PROFILE ] Per bag 5 g.

5. Degree of friability

The method comprises the following steps: and (3) putting 20g of the thesium particle preparation obtained in the examples 1-3 and 25 glass beads with the diameter of 7mm into a friability apparatus, rotating for 100 times, collecting, sieving by a 40-mesh sieve, weighing the weight of particles on the sieve, and calculating the weight loss percentage of the particles.

6. Stability of

The method comprises the following steps: the thesium particle preparations obtained in the examples 1 to 3 were subjected to a long-term stability test under a packaging condition of the market, and the temperature was 25 ℃. + -. 2 ℃, the relative humidity was 60%. + -. 5%, and the contents were sampled and detected at the end of 0, 3, 6, 9, 12, 18, and 24 months, respectively.

And (4) analyzing results:

physicochemical property tests were performed on the thesium particle preparations obtained in examples 1 to 3, wherein the test items in the quality standard included properties, identification, moisture, particle size, and content, and the result analysis is shown in table 1 below, and the thesium particle preparations obtained in examples 1 to 3 were all yellow-brown particles; smell, sweet taste, slight bitter taste; the method meets the specification, the friability is 16.0-16.8%, the disintegration time is 16-17 minutes, the water content is 2-2.2%, the particle size is less than or equal to 8, and the degradation rate of the total flavone after 24 months in a stability test is 0.96-1.06%.

In summary, based on the preparation method of the thesium Chinese granular preparation and the thesium Chinese granular preparation obtained by the preparation method according to the component proportion provided by the application, the preparation method is an improvement of the traditional preparation method of the thesium Chinese granular preparation, the thesium Chinese extract solution, the binder and the lubricant are mixed and then granulated by adopting a spray drying preparation method, and meanwhile, the thesium Chinese granular preparation with excellent properties is obtained by twice sieving treatment. The preparation process of spray drying is simple, the drying is mild, the particle size distribution of the obtained particles is narrow, and meanwhile, the active ingredients in the solid dispersion of the prepared thesium chinense particle preparation are uniformly dispersed mainly in an amorphous form and have higher Gibbs energy, so that the energy required for dissolving is less, the solubility of the active ingredients such as total flavonoids of the thesium chinense particle preparation can be greatly improved, the use effect is improved, and the application range of the thesium chinense particle preparation is expanded.

TABLE 1

The above description is only exemplary of the present application and should not be taken as limiting the present application, as any modification, equivalent replacement, or improvement made within the spirit and principle of the present application should be included in the protection scope of the present application.