CN112263551A

CN112263551A - Spleen-tonifying and digestion-improving composition granules with excellent taste and preparation method thereof

Info

Publication number: CN112263551A
Application number: CN202011186603.7A
Authority: CN
Inventors: 梅勇; 张传辉; 郭娟; 粟冲; 李婷; 谭东丽; 王明杰; 罗磊
Original assignee: Chongqing Hilan Pharmaceutical Co ltd
Current assignee: Chongqing Hilan Pharmaceutical Co ltd
Priority date: 2020-10-30
Filing date: 2020-10-30
Publication date: 2021-01-26

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to spleen-tonifying and digestion-improving composition granules with excellent taste and a preparation method thereof. The spleen-tonifying and clearing composition granules with good mouthfeel comprise the following raw materials in parts by weight: 27-35 parts of dry paste powder, 55-70 parts of filler, 0.3-0.6 part of sweetener, 0.2-0.6 part of sour agent, 0.2-0.6 part of isotonic regulator and 0.8-1.1 part of pH value regulator; the raw materials of the dry paste powder comprise radix codonopsitis, lotus seed, white hyacinth bean, coptis root, scutellaria baicalensis, honeysuckle, medicinal fermented mass, hawthorn, stir-baked plantain seed and dried ginger. The technical problems that the spleen invigorating and clearing granule is poor in taste and bitter taste is difficult to cover are solved by simultaneously adding the filler, the sweetening agent, the sour agent and the isoosmotic adjusting agent. The method can be applied to the taste research of medicinal preparations, and can improve social benefits.

Description

Spleen-tonifying and digestion-improving composition granules with excellent taste and preparation method thereof

Technical Field

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to spleen-tonifying and digestion-improving composition granules with excellent taste and a preparation method thereof.

Background

The spleen-invigorating and heat-clearing granule (original name: spleen-invigorating and diarrhea-checking granule) is a national Chinese medicine protection variety, is prepared by combining 10 traditional Chinese medicinal materials of codonopsis pilosula, lotus seed, white hyacinth bean, coptis root, scutellaria baicalensis, honeysuckle, hawthorn, plantain seed (stir-fried with salt), medicinal fermented mass, dried ginger and the like, and has the effects of clearing heat and removing dampness, invigorating spleen and checking diarrhea, resolving food stagnation and removing food stagnation and the like. Can be used for treating infantile diarrhea and dyspepsia due to spleen deficiency and damp-heat. In the formula, coptis chinensis is added, and the berberine hydrochloride exists in a finished product medicament in a form of berberine hydrochloride after extraction, and as is known, the berberine hydrochloride is a very bitter substance, and the problem of the taste of the product is difficult to solve by using one or more sweetening agents or other prior arts. At present, the product adopts stevia as a sugar-free particle prepared by a flavoring agent. Chinese patent: a composition for treating children's spleen deficiency and damp-heat and its preparation method (patent No. CN101461932B) use cane sugar as corrective to make sugar type granule, the corrective used of these two kinds of granule can't realize the good taste-modifying at all, cause the product to be extremely bitter in mouthfeel, children's taking can't lower the pharynx at all, it is extremely bad to take medicine, and the granule prepared in the prior art is very hard, its dissolubility is very bad, the dissolution extraction of the marker ingredient of dissolubility detection brings the very big trouble, it is not obvious to distinguish, and cause the marker ingredient to dissolve out slowly too, may cause the human body to absorb slowly, the bioavailability is low, can't fully guarantee the curative effect of the product.

In the aspect of taste correction, the existing patent technology (CN1273133C taste-masking berberine hydrochloride particles and preparations thereof) adopts EPO (acrylic resin combined coating liquid) or a literature report that the berberine is coated by acrylic resin IV to mask the bitter taste of the berberine hydrochloride, but the technology has high requirements on equipment (a fluidized bed), takes long time, easily generates static electricity, is adhered to the wall of the fluidized bed, is not mature in technology and difficult to industrialize, and EPO or acrylic resin IV is expensive in price, belongs to a traditional Chinese medicine mixed extract, is prepared into particles, is finally dissolved in an aqueous solution for taking, breaks the coating in the dissolving process, cannot mask the bitter taste, is obviously unsuitable for the coating taste-masking method, and is also not beneficial to the industrialized production of the product. In the prior art, one or a plurality of combinations of sucrose, stevioside, saccharin sodium, sodium cyclamate, aspartame, sucralose and the like are adopted to cover the bitter taste of berberine, but the effect is not obvious. The product belongs to children medicine, has the effects of clearing heat and removing dampness, strengthening spleen and stopping diarrhea, resolving food stagnation and removing food retention, has obvious curative effect on treating diarrhea and dyspepsia caused by spleen deficiency and damp-heat in children, and is high in safety, but the application of the product is limited by the problems of taste, dissolubility and dissolution rate.

Disclosure of Invention

The invention aims to provide spleen-tonifying and clearing composition granules with excellent taste, and aims to solve the technical problems that the spleen-tonifying and clearing granules are poor in taste and difficult in bitterness covering.

In order to achieve the purpose, the invention adopts the following technical scheme:

a spleen-invigorating and digestion-improving composition granule with excellent taste comprises the following raw materials: bitter taste masking compositions and active ingredients; the bitter taste masking composition comprises the following components in parts by weight: 55-70 parts of filler, 0.3-0.6 part of sweetener, 0.2-0.6 part of sour agent, 0.2-0.6 part of isoosmotic adjusting agent and 0.8-1.1 part of pH value adjusting agent.

The principle and the beneficial effects of the technical scheme are as follows: the spleen-tonifying and clearing composition granules with excellent mouthfeel are added with the filler, the sweetening agent, the sour agent, the isotonic regulator (also called as salty agent) and the pH value regulator, so that the bitter taste of the medicine is well covered, and the spleen-tonifying and clearing composition granules are suitable for children to take. 3g of the product is dissolved in 20-30 ml of warm boiled water and then is orally taken, the taste buds feel comfortable sour firstly in the taking process, and then sweet taste and salty taste are obtained, the stimulation of the bitter taste to the taste buds can be reduced because the prepared liquid medicine and the taste bud tissue liquid are basically isotonic, and the taste buds cannot feel obvious bitter taste in the swallowing process.

The formula harmonizes the mouthfeel of the preparation from three aspects (sour, sweet and salty). In the process of taking the medicine, the sour agent contacts with the taste buds to form countless target spots to seal the taste buds so as to prevent the invasion of bitter taste; adding sweetener to neutralize bitter taste; the addition of isotonic regulator (such as sodium chloride) can ensure that the prepared medicinal liquid and the tissue liquid of taste bud are isotonic, prevent the medicinal liquid from quickly diffusing to taste bud, and reduce the stimulation of bitter taste to taste bud. The addition of isotonic regulators such as sodium chloride can also feel a comfortable salty taste, so that the product tastes sour, sweet, salty and delicious, has no obvious bitter taste, and enhances the medicine taking compliance of children.

In addition, the inventor unexpectedly finds that after the sweetening agent, the sour agent and the isoosmotic adjusting agent are added, the solubility of the marker components of the medicine is improved, so that the identification is more obvious, the dissolubility and the dissolution speed of the prepared granules are high, the detection, the extraction and the taking and blending are convenient, the bioavailability is improved, and the curative effect of the product is ensured.

The beneficial effects of the technical scheme are summarized as follows: the scheme adopts the common, safe and good auxiliary material combination to solve the clinical application bottleneck that the spleen-invigorating and clearing composition granules have bitter taste, can greatly improve the medicine taking compliance of children, and enlarges the clinical application range. The scheme also obtains the additional effect of increasing the solubility of the functional components (such as berberine hydrochloride and the like) by improving the formula components.

Further, the effective components comprise dry paste powder; the weight ratio of the dry paste powder to the filler is 27-35: 55-70 parts; the raw materials of the dry paste powder comprise radix codonopsitis, lotus seed, white hyacinth bean, coptis root, scutellaria baicalensis, honeysuckle, medicinal fermented mass, hawthorn, stir-baked plantain seed and dried ginger.

By adopting the technical scheme, the dry paste powder contains the functional components (bitter substances) of the medicine, and the bitter masking composition can better mask the bitter taste of the medicine.

Further, the filler is one or a mixture of a plurality of soluble starch, xylitol, mannitol and lactose.

By adopting the technical scheme, the filler is added, the diluted medicinal powder is convenient to granulate, and the fresh and cool sweet taste is achieved, so that the mouthfeel is improved.

Further, the sour agent is one or a mixture of more of citric acid, fumaric acid and tartaric acid; the sweetener is one or a mixture of more of stevioside, saccharin sodium, sodium cyclamate, aspartame and sucralose.

By adopting the technical scheme, the organic acid belongs to common auxiliary materials in medicinal preparations, has high safety and can better improve the mouthfeel of the medicine. The sweetening agent belongs to common auxiliary materials in pharmaceutical preparations, has high safety and can better improve the mouthfeel of the medicine.

Further, the isotonic regulator is sodium chloride and/or sodium bicarbonate; the pH value regulator is sodium citrate and/or sodium acetate

By adopting the technical scheme, the isotonic regulator belongs to common auxiliary materials in medicinal preparations, has high safety, can feel a comfortable salty taste when added, and enhances the taste improvement effect.

Further, the filler is a mixture consisting of soluble starch and mannitol; the sweetener is sucralose or stevioside; the sour agent is citric acid; the isotonic regulator is sodium chloride; the pH value regulator is sodium citrate.

By adopting the technical scheme, citric acid is preferably selected as the acidity regulator, sucralose and stevioside are preferably selected as the sweetening agent, and sodium chloride is preferably selected as the isotonic and salty taste regulator. Experiments prove that the effect of improving the mouthfeel is optimal by using the substances in combination.

Further, 3g of the spleen-invigorating and digestion-improving composition granules are dissolved in 20 to 30ml of water to obtain a composition solution, and the pH value of the composition solution is 5.0 to 6.0.

By adopting the technical scheme, the spleen-tonifying and clearing composition granules prepared by the scheme can obtain better mouthfeel when the pH value is 5.0-6.0 after being dissolved in water.

Further, a preparation method of the spleen-tonifying and clearing composition granules with excellent taste comprises the following steps:

(1) preparation of dry paste powder: mixing radix Codonopsis, semen Nelumbinis, semen lablab album, Coptidis rhizoma, Scutellariae radix, flos Lonicerae, Massa Medicata Fermentata, fructus crataegi, semen plantaginis processed with salt and Zingiberis rhizoma to obtain medicinal mixture, extracting effective components from the medicinal mixture with water as extraction solvent to obtain extract, and drying to obtain dry extract powder;

(2) pulverizing to obtain dry extract powder and filler;

(3) dissolving a sweetening agent, an acidulant, an isotonic regulator and a pH regulator in water to obtain a wetting agent;

(4) mixing the pulverized dry extract powder, pulverized filler and wetting agent, and granulating to obtain the composition granule.

By adopting the technical scheme, the functional components in the medicinal materials can be obtained by water extraction, and the dry paste powder containing the functional components is mixed with other ingredients to prepare the medicinal granules with excellent mouthfeel.

Further, in the step (1), the effective components in the medicinal material mixture are extracted three times by using water as an extraction solvent to obtain combined filtrate, and the volume of the combined filtrate is concentrated to be one fourth of the original volume to obtain the extract.

By adopting the technical scheme, the extraction is carried out for multiple times, and the extraction rate of the effective components is ensured.

Further, in the step (2), the particle diameters of the crushed dry paste powder and the crushed filler are both less than 150 microns.

By adopting the technical scheme, the particle diameters of the crushed dry paste powder and the crushed filler are both less than 150 microns, so that the mixing uniformity of the product is greatly improved.

Drawings

FIG. 1 is a statistical chart of particle size distribution (spleen-invigorating and clearing dry paste powder) of Experimental example 1 of the present invention.

FIG. 2 is a statistical graph of the particle size distribution (soluble starch) of Experimental example 1 of the present invention.

FIG. 3 is a particle size distribution statistical chart (mannitol) of Experimental example 1 of the present invention.

Detailed Description

The present invention will be further described with reference to specific examples, but it should not be construed that the scope of the above-described subject matter of the present invention is limited to the examples. All the technologies implemented based on the above-mentioned contents of the present invention belong to the scope of the present invention. The following examples can be replaced by, reduced by, or increased by pharmaceutically acceptable adjuvants of the same type.

Example 1: spleen-tonifying and digestion-improving composition granule with improved taste

(1) Preparation of spleen-invigorating and digestion-improving composition granules

36 parts of codonopsis pilosula, 36 parts of lotus seeds, 54 parts of white hyacinth beans, 18 parts of coptis chinensis, 36 parts of scutellaria baicalensis, 36 parts of honeysuckle, 36 parts of medicinal fermented mass, 36 parts of hawthorn, 36 parts of semen plantaginis (roasted with salt) and 18 parts of rhizoma zingiberis are decocted with water for three times, drinking water with the amount of 8 times of that of decoction pieces is added for the first time, after the drinking water is soaked for 30 minutes, a steam valve is opened, the boiling is carried out for 1 hour, liquid medicine is discharged, the liquid medicine is filtered through a 100-mesh duplex filter, and the. Adding 8 times of drinking water, opening steam valve, heating to boil for 1 hr, discharging medicinal liquid, filtering with 100 mesh duplex filter, and storing the filtrate in storage tank. Adding drinking water 6 times the amount of the decoction pieces for the third time, opening a steam valve, heating to boil for 1 hr, discharging the medicinal liquid, filtering with a 100-mesh duplex filter, and storing the filtrate in a storage tank. Mixing filtrates, concentrating to remove three-fourths of water in a double-effect concentrator, and drying with a spray drying tower to obtain dry extract powder.

(2) Preparation of spleen-tonifying and digestion-improving composition granules with improved taste

In this example, the taste of the spleen-invigorating and clearing composition granule is improved according to formula 1, wherein formula 1 is as follows:

the spleen-invigorating and digestion-clearing composition granules are prepared according to a formula 1, and the preparation process comprises the following specific steps:

the first step is as follows: pulverizing and sieving dry extract powder with granularity less than 150 μm, mannitol, and soluble starch.

The second step is that: the sweetening agent, the sour agent, the isoosmotic adjusting agent and the pH value adjusting agent in the prescription amount are taken, and are dissolved in a proper amount of purified water to be used as the wetting agent.

The third step: taking dry paste powder, soluble starch and mannitol according to the prescription amount, adding into a high-efficiency wet mixing granulator, adding a wetting agent, stirring, preparing a soft material, granulating with a 16-mesh sieve, drying in a boiling dryer, granulating, adding into a three-dimensional motion mixer, mixing for 15-30 minutes, and packaging (3 g/bag) to obtain the spleen-tonifying clearing granule.

Example 2:

in this example, the taste of the spleen-invigorating and clearing composition granule is improved according to formula 2, wherein formula 2 is as follows:

the spleen-invigorating and clearing composition granules are prepared according to the formula 2, and the specific preparation process is shown in example 1.

Example 3:

this exampleThe taste of the spleen-invigorating and clearing composition granules is improved according to the formula 3, wherein the formula 3 comprises the following components:

the spleen-invigorating and clearing composition granules are prepared according to the formula 3, and the specific preparation process is shown in example 1.

Example 4:

in this example, the taste of the spleen-invigorating and clearing composition granule is improved according to formula 4, wherein formula 4 is as follows:

the spleen-invigorating and clearing composition granules are prepared according to the formula 4, and the specific preparation process is shown in example 1.

Example 5:

in this example, the taste of the spleen-invigorating and clearing composition granule is improved according to formula 5, wherein formula 5 is as follows:

the spleen-invigorating and clearing composition granules are prepared according to the formula 5, and the specific preparation process is shown in example 1.

Example 6:

in this example, the taste of the spleen-invigorating and clearing composition granule is improved according to formula 6, wherein formula 6 is as follows:

the spleen-invigorating and clearing composition granules are prepared according to the formula 6, and the specific preparation process is shown in example 1.

Comparative example 1

Referring to patent CN101461932B (a pharmaceutical composition for treating infantile diarrhea due to spleen deficiency and damp-heat and its preparation method), sucrose is used as correctant and filler to prepare spleen invigorating and clearing granule.

The comparative example improves the mouthfeel of the spleen invigorating and clearing composition granules according to comparative formula 1, wherein the comparative formula 1 comprises the following components:

spleen-invigorating and digestion-promoting extract 220.0 kg (about 88.0 kg dry extract)

Dextrin 106.0 kg

106.0 kg of sucrose

The spleen-invigorating and clearing composition granules are prepared according to a comparative formula 1, and the specific preparation process is as follows:

the first step is as follows: the spleen-invigorating and clearing extract (i.e., the extract obtained after three quarters of the water content is concentrated in a double-effect concentrator without using a spray drying tower to obtain dry extract powder) is prepared according to example 1 for later use.

The second step is that: pulverizing sucrose and dextrin, and sieving with 100 mesh sieve.

A third part: taking the extract, sucrose and dextrin according to the prescription amount, adding the extract, the sucrose and the dextrin into a high-efficiency wet mixing granulator, stirring, preparing a soft material, granulating by using a 16-mesh sieve, drying in a boiling dryer, granulating, adding into a three-dimensional motion mixer, mixing for 15-30 minutes, and packaging (3 g/bag) to obtain the spleen-tonifying clearing granule.

Comparative example 2

The sugar-free formula is approved at present, dextrin and starch are used as fillers, and stevioside is used as a flavoring agent to prepare the spleen-invigorating and clearing granule. The comparative example improves the mouthfeel of the spleen invigorating and clearing composition granules according to comparative formula 2, and comparative formula 2 is as follows:

the spleen-invigorating and clearing composition granules are prepared according to a comparative formula 2, and the specific preparation process is as follows:

the first step is as follows: the spleen-invigorating and clearing extract is prepared according to example 1 for later use.

The second step is that: pulverizing starch and dextrin, and sieving with 100 mesh sieve.

The third step: taking the extract, starch, dextrin and stevioside according to the prescription amount, adding the extract, the starch, the dextrin and the stevioside into a high-efficiency wet mixing granulator, stirring, preparing a soft material, granulating by using a 16-mesh sieve, drying in a boiling dryer, granulating, adding into a three-dimensional motion mixer, mixing for 15-30 minutes, and packaging (3 g/bag) to obtain the spleen-tonifying clearing granule.

Comparative example 3

Referring to patent CN200410090676.0(CN1273133C taste-masked berberine hydrochloride granules and formulations thereof), the dry extract powder prepared in example 1 was wetted with ethanol, sieved through a 60-mesh sieve to prepare fine granules, and after drying and size stabilization, 13% EPO (acrylic resin combined coating solution) was sprayed onto the fine granules by a fluidized bed coating technique to prepare a taste-masked ointment, which tasted the coated fine granules, and the bitter taste immediately after the taste was less than that without the coating, but after a while, a noticeable bitter taste was felt.

The comparative example improves the mouthfeel of the spleen invigorating and clearing composition granules according to comparative formula 3, wherein the comparative formula 3 comprises the following components:

spleen-invigorating and clearing EPO coated taste-masking fine granule 90.4 kg

20 kg of sucrose

Sucralose 1.6 kg

The spleen-invigorating and clearing composition granules are prepared according to a comparative formula 3, and the specific preparation process is as follows:

the first step is as follows: pulverizing sucrose, and sieving with 100 mesh sieve.

The second step is that: adding the spleen-tonifying and clearing EPO coating taste-masking fine granules and cane sugar into a high-efficiency wet mixing granulator, adding a proper amount of 50% ethanol solution for wetting, stirring to prepare a soft material, granulating by using a 16-mesh sieve, drying in a boiling dryer, finishing granules, adding into a three-dimensional motion mixer, mixing for 15-30 minutes, and packaging (3 g/bag) to obtain the spleen-tonifying and clearing granules.

Comparative example 4

The comparative example improves the mouthfeel of the spleen invigorating and clearing composition granules according to comparative formula 4, wherein the comparative formula 4 comprises the following components:

the spleen-invigorating and clearing composition granules are prepared according to a comparative formula 4, and the specific preparation process is as follows:

The second step is that: the sweetening agent with the prescription amount is taken, and is dissolved in a proper amount of purified water to be used as a wetting agent.

Comparative example 5

The comparative example improves the mouthfeel of the spleen invigorating and clearing composition granules according to comparative formula 5, wherein the comparative formula 5 comprises the following components:

the spleen-invigorating and clearing composition granules are prepared according to a comparative formula 5, and the specific preparation process is as follows:

The second step is that: the sweetening agent and the sour agent with the prescription amount are taken, and are dissolved in a proper amount of purified water to be used as the wetting agent.

Comparative example 6

The comparative example improves the mouthfeel of the spleen invigorating and clearing composition granules according to comparative formula 6, and comparative formula 6 is as follows:

the spleen-invigorating and clearing composition granules are prepared according to a comparative formula 6, and the specific preparation process is as follows:

The second step is that: the sweetening agent and the isotonic agent with the prescription amount are taken, and are dissolved in a proper amount of purified water to be used as the wetting agent.

Comparative example 7

This comparative example is substantially the same as example 1 except that no pH adjuster is used, and comparative formula 7 is as follows:

comparative example 8

This comparative example is substantially the same as example 1 except that no pH adjuster is used, and comparative formula 8 is as follows:

experimental example 1: detection of particle size of raw and auxiliary materials

In this experimental example, the raw material spleen-invigorating digestion dry paste powder (see the preparation method of example 1), soluble starch and mannitol were examined, and in this scheme, the spleen-invigorating digestion dry paste powder, soluble starch and mannitol were pulverized into a form requiring a particle size of less than 150 μm. The results are shown in Table 1.

Table 1: results of particle size analysis

The test result shows that the particle sizes of the ointment and the filler are both within 150 microns, which is helpful for uniform mixing, and the particle size distribution is shown in figures 1-3.

Experimental example 2: taste and pH detection

According to the method for taking the product, each bag (3 g/bag) is heated with 30ml of warm boiled water, stirred and dissolved for pH value measurement, and the results are shown in Table 2.

Table 2: results of pH measurement

According to the provisions of GB/T16291.2-2010 (sensory analysis selection, training and management evaluator general guide 2 part: expert evaluator), a plurality of recruiters are recruited from society, training and testing are carried out on the recruiters according to the standards, and finally 10 sensory evaluators are formed, wherein 5 males (the average age is 31.4 +/-3.6 years) and 5 females (the average age is 32.8 +/-5.8 years).

According to the method for taking the product, each bag (3 g/bag) is heated with 30ml of warm boiled water, dissolved and mixed uniformly to form test liquid medicine, and 10 sensory evaluation personnel evaluate the taste of the prescriptions 1-6 and the comparative prescriptions 1-8. The evaluation method was that the sensory evaluation persons restricted the diet within 2 hours before the start of the experiment and could not ingest foods that were highly irritating or taste-affecting. In the tasting process, 10ml of test liquid medicine is placed in a test cup, a sensory evaluation person completely contains 10ml of test liquid medicine in an inlet, the test liquid medicine stays at the root of the tongue for 5 seconds, and then the test liquid medicine is spitted out. There should be an interval (10min) between each test evaluation to avoid cross-talk. After tasting was complete, sensory evaluators scored according to the criteria of table 3, and the taste evaluation results are detailed in table 4.

Table 3: evaluation criteria for bitterness

Numbering	Description of mouthfeel	Score of
			1	Extremely bitter and unacceptable	7-10
2	Bitter and unacceptable	4-7
			3	Slightly bitter and acceptable	2-4
4	Almost no bitter taste	0-2

Table 4: evaluation results of bitterness

The sensory assessor's assessment of formula 1 is generally: the taste is sour and comfortable, and the taste is salty, sweet and tasty. The evaluation of prescription 2 was generally: the taste is sour, the taste is salty, sweet and tasty, and the sour taste is not authentic but can be accepted; sour, salty, sweet and tasty. The general evaluation of formula 3 was sour, salty, sweet, refreshing, and not authentic, but acceptable. The general evaluation for prescription 4 was: the taste is sour and comfortable, and the taste is salty, sweet and tasty, and can be accepted. The general evaluation for prescription 5 was: the taste is sour and comfortable, and the taste is salty and sweet and can be accepted. The general evaluation of formula 6 was sour and pleasant in taste, salty and sweet. The general evaluation of comparative prescription 1 was: the taste was extremely bitter and unacceptable. The general evaluation of comparative prescription 2 was: sweet, bitter and lasting in bitterness, which is unacceptable. The general evaluation of comparative prescription 3 was: sweet, bitter and lasting in bitterness, which is unacceptable. The general evaluation of comparative prescription 4 was: the taste is immediately bitter after sweet and sour, and is unacceptable. The general evaluation of comparative prescription 5 was: sweet, bitter and lasting in bitterness, which is unacceptable. The general evaluation of comparative prescription 6 was: the taste is slightly salty, bitter and lasting, and the taste is unacceptable; the mouthfeel of both comparative formulas 7 and 8 was considered slightly bitter in taste, but was acceptable.

Test results show that the combination of a certain amount of organic acid, a certain amount of edible salt and a certain amount of sweetener can well cover the extremely bitter taste of berberine hydrochloride and the like, the mouthfeel of citric acid is best in the aspect of organic acid selection, the mouthfeel of stevioside and sucralose in the aspect of sweetener selection is best, the mouthfeel of sodium chloride in the aspect of isotonic and salty taste conditioning agent selection is good, the pH value is adjusted to be within the range of 5.0-6.0, and the mouthfeel is best.

Experimental example 3: dissolution rate determination of berberine hydrochloride

The

recipes

1 and 6 with good mouthfeel and the comparative recipes 1 to 6 are subjected to detection and comparison research.

1) Taking 1 bag (3 g/bag) of the product, taking 900ml of water, pH1.2, pH4.0 and pH6.8 phosphate buffer solution as dissolution medium according to a dissolution rate and release rate determination method (0931 second method of the four-part general rule of Chinese pharmacopoeia 2015 edition), controlling the temperature to be 37 +/-0.5 ℃, degassing the dissolution medium at 50rpm, sampling 10ml (adding isothermal equal-volume dissolution medium) at 5, 10, 15, 30, 45 and 60min respectively, filtering, and taking the subsequent filtrate as a test solution. Taking a proper amount of berberine hydrochloride reference substance, dissolving with corresponding dissolution medium, making into solution containing berberine hydrochloride 5 μ g per 1ml, and shaking to obtain reference substance solution.

Chromatographic conditions and system applicability test: a column of C18 (Waters Xterra C18, 4.6X 250 mm; 5 μm); potassium dihydrogen phosphate and acetonitrile at 0.05mol/L (78: 22); flow rate: 1.0 ml/min; column temperature: 25 ℃; detection wavelength: 263 nm; sample introduction amount: 20 mu l, under the chromatographic condition, the berberine hydrochloride has sharp peak shape, the theoretical plate number is 3000 according to the berberine hydrochloride, and the separation degree of the main peak of the berberine and other adjacent mixed peaks is more than 1.5.

And (3) determination: taking the test solution and the control solution, performing sample injection detection according to high performance liquid chromatography (China pharmacopoeia 2015 edition four parts general rule 0512), and calculating the cumulative percent dissolution (remark: the marked content is the average content of berberine hydrochloride) of each bag at different sampling time according to an external standard method. The results are shown in tables 5 to 8.

Table 5: measurement of dissolution Curve in Water (mean. + -. SD, n ═ 6)

Serial number

5 minutes (%)

10 minutes (%)

15 minutes (%)

30 minutes (%)

45 minutes (%)

60 minutes (%)

Prescription 1

96±3.2

97±2.4

96±2.1

98±1.8

98±2.3

98±1.9

Prescription 6

95±3.4

96±2.7

98±2.5

98±2.3

99±2.6

98±1.8

Comparative prescription 1

62±6.7

85±5.8

96±3.2

97±2.8

97±2.4

98±2.0

Comparative prescription 2

59±7.5

84±6.4

97±4.1

98±3.6

98±2.6

99±1.5

Comparative prescription 3

35±9.4

64±8.1

71±4.6

82±3.5

83±3.1

84±2.8

Comparative prescription 4

80±6.2

89±4.1

91±3.2

92±2.7

91±2.3

92±1.8

Comparative prescription 5

94±3.2

96±2.4

98±2.1

97±2.3

98±1.9

99±1.2

Comparative prescription 6

80±3.6

88±2.2

91±2.9

96±2.0

98±1.8

98±1.6

Table 6: measurement of dissolution Curve in hydrochloric acid solution at pH1.2 (mean. + -. SD, n. gtoreq.6)

Serial number

5 minutes (%)

10 minutes (%)

15 minutes (%)

30 minutes (%)

45 minutes (%)

60 minutes (%)

Prescription 1

81±2.6

90±2.9

91±2.3

94±2.2

95±1.9

95±1.6

Prescription 6

79±3.8

89±3.0

92±2.5

93±2.1

94±1.8

94±1.5

Comparison ofPrescription 1

30±8.9

65±4.6

82±3.1

89±2.5

91±2.7

92±6.7

Comparative prescription 2

34±7.6

62±5.6

84±3.5

91±2.8

92±2.1

93±1.8

Comparative prescription 3

15±6.4

36±5.4

67±3.1

71±3.1

73±2.9

75±2.1

Comparative prescription 4

71±4.4

76±4.1

83±3.6

87±2.4

89±2.0

90±1.9

Comparative prescription 5

76±2.2

88±4.5

90±3.0

94±2.6

95±2.1

95±2.0

Comparative prescription 6

66±5.6

75±4.7

84±3.2

86±2.8

89±2.4

90±1.9

Table 7: measurement of dissolution Curve in phosphate buffer at pH4.0 (mean. + -. SD, n. gtoreq.6)

Table 8: measurement of dissolution Curve in phosphate buffer at pH6.8 (mean. + -. SD, n. gtoreq.6)

Serial number

5 minutes (%)

10 minutes (%)

15 minutes (%)

30 minutes (%)

45 minutes (%)

60 minutes (%)

Prescription 1

95±2.9

96±2.6

97±2.5

98±2.1

98±1.8

99±1.6

Prescription 6

97±3.1

98±2.9

98±2.4

98±2.3

99±2.0

98±1.9

Comparative prescription 1

68±6.3

85±5.1

96±3.2

97±2.7

97±2.1

98±1.8

Comparative prescription 2

66±6.1

84±5.2

97±4.2

98±3.7

98±2.8

99±1.7

Comparative prescription 3

57±5.9

70±5.1

85±4.3

88±3.1

89±2.4

90±2.0

Comparative prescription 4

80±4.6

83±3.7

88±3.1

92±2.6

91±2.1

93±1.6

Comparative prescription 5

94±3.1

95±2.8

97±2.6

98±2.4

98±1.9

98±1.6

Comparative prescription 6

81±4.7

84±3.9

89±3.6

93±2.4

92±2.0

93±1.8

The measurement result shows that:

formulations

1 and 6 in example 1 have very ideal dissolution effect in water, hydrochloric acid solution at ph1.2, phosphate buffer solution at ph4.0 and ph6.8, and can dissolve very quickly, compared with

formulations

1 and 2, because the particles are hard, the dissolution effect in the first 10 minutes is inferior to that of the product of the experimental process, compared with formulation 3, after EPO coating, the dissolution of the whole is slow, the dissolution of each point is low, and compared with

formulations

4 and 6, because no sour taste modifier (citric acid) is added, no good dissolution effect is obtained, and the dissolution is slightly low. Compared with the prescription 5, the sour taste modifier (citric acid) is added, so that the dissolution effect is better. The comparative analysis and research result shows that the dissolution of the particles can be improved by matching the spray-dried loose dry paste powder with the taste regulating substance, so that the dissolution rate and the total dissolution amount of the marked components can be increased.

Experimental example 4: physical and chemical index detection

The

recipes

1 and 6 and the

comparative recipes

1 and 6 with the best mouthfeel are selected for detection and comparison studies by referring to the quality standard (standard number: WS1-1094(ZD-0941) -2002-2011Z) of the spleen-invigorating and digestion-relieving granules, and the results are shown in tables 9 and 10.

Table 9: results of physical and chemical preparation evaluation

Table 10: results of physical and chemical preparation evaluation (Table 9)

As can be seen from the data in tables 9 and 10, the spleen-invigorating and digestion-improving granules prepared according to the scheme and having good taste better meet the quality standard requirements of the spleen-invigorating and digestion-improving granules.

The foregoing is merely an example of the present invention and common general knowledge in the art of designing and/or characterizing particular aspects and/or features is not described in any greater detail herein. It should be noted that, for those skilled in the art, without departing from the technical solution of the present invention, several variations and modifications can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicability of the patent. The scope of the claims of the present application shall be determined by the contents of the claims, and the description of the embodiments and the like in the specification shall be used to explain the contents of the claims.

Claims

1. A spleen-invigorating and digestion-improving composition granule with excellent taste is characterized by comprising the following raw materials: bitter taste masking compositions and active ingredients; the bitter taste masking composition comprises the following components in parts by weight: 55-70 parts of filler, 0.3-0.6 part of sweetener, 0.2-0.6 part of sour agent, 0.2-0.6 part of isoosmotic adjusting agent and 0.8-1.1 part of pH value adjusting agent.

2. The spleen-invigorating and digestion-improving composition granule with excellent taste according to claim 1, wherein the medicinal ingredient comprises dry extract powder; the weight ratio of the dry paste powder to the filler is 27-35: 55-70 parts; the raw materials of the dry paste powder comprise radix codonopsitis, lotus seed, white hyacinth bean, coptis root, scutellaria baicalensis, honeysuckle, medicinal fermented mass, hawthorn, stir-baked plantain seed and dried ginger.

3. The spleen-invigorating and refreshing composition granule with excellent taste according to claim 2, wherein the filler is one or a mixture of soluble starch, xylitol, mannitol and lactose.

4. The spleen-invigorating and cleansing composition granule with excellent taste according to claim 3, wherein the sour agent is one or a mixture of more of citric acid, fumaric acid and tartaric acid; the sweetener is one or a mixture of more of stevioside, saccharin sodium, sodium cyclamate, aspartame and sucralose.

5. The spleen-invigorating and cleansing composition granule with excellent mouthfeel according to claim 4, wherein the isotonic regulator is sodium chloride and/or sodium bicarbonate; the pH value regulator is sodium citrate and/or sodium acetate.

6. The spleen-invigorating and cleansing composition granule with excellent mouthfeel according to claim 5, wherein the filler is a mixture of soluble starch and mannitol; the sweetener is sucralose or stevioside; the sour agent is citric acid; the isotonic regulator is sodium chloride; the pH value regulator is sodium citrate.

7. The spleen-invigorating cleansing composition granule with excellent mouthfeel according to claim 6, wherein 3g of the spleen-invigorating cleansing composition granule is dissolved in 20 to 30ml of water to obtain a composition solution, and the pH value of the composition solution is 5.0 to 6.0.

8. The method for preparing spleen-invigorating and cleansing composition granules with excellent mouthfeel according to any one of claims 1 to 7, which comprises the following steps:

(2) pulverizing to obtain dry extract powder and filler;

9. The method for preparing spleen-invigorating and digestion-improving composition granules according to claim 8, wherein in step (1), the effective ingredients in the mixture of medicinal materials are extracted three times using water as an extraction solvent to obtain a combined filtrate, and the volume of the combined filtrate is concentrated to one fourth of the original volume to obtain an extract.

10. The method for preparing spleen-invigorating and digestion-improving composition granules with excellent taste according to claim 9, wherein the method comprises the following steps: in the step (2), the particle diameters of the crushed dry paste powder and the crushed filler are both less than 150 microns.