Sugar-free compound honeysuckle granules and preparation method thereof

Abstract

The invention relates to the technical field of preparation methods of traditional Chinese medicine preparations, in particular to sugar-free compound honeysuckle granules and a preparation method of the sugar-free compound honeysuckle granules. The preparation method comprises the following steps: weighing an excipient of which the mass is 0.8-3.6 times of the total mass of a honeysuckle distilled extract, a honeysuckle extract and a scutellaria baicalensis and fructus forsythiae extract; stevioside accounting for 0.43-0.45% of the total mass of the honeysuckle distilled extract, the honeysuckle extract and the scutellaria baicalensis and fructus forsythiae extract is weighed, and the excipient comprises one or more of dextrin, sodium carboxymethyl cellulose and mannitol; uniformly mixing the honeysuckle distilled extract, the honeysuckle extract, the scutellaria baicalensis and fructus forsythiae extract with the excipient and the stevioside to prepare wet granules; and drying and finishing the wet granules, and subpackaging to obtain the finished sugar-free compound honeysuckle granules. The sugar-free honeysuckle granules prepared by the method can have good dissolubility at low temperature, are high in content of active ingredients, maintain the unique faint scent of honeysuckle to a certain extent, and are easily accepted by wider patient groups.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmacy, and particularly relates to a sugar-free compound honeysuckle granule and a preparation method thereof. Background Art

[0002] Compound honeysuckle granules are composed of three Chinese medicines: honeysuckle, forsythia, and scutellaria. They have the effects of clearing heat and detoxifying, cooling blood and reducing swelling. They are used for wind-heat cold, pharyngitis, tonsillitis, eye pain, toothache, and carbuncle. Because the drug tastes bitter and cold, it is necessary to add an appropriate amount of sweetener to improve the patient's compliance with medication. However, the commonly used sweetener sucrose is very limited in clinical applications for some patients with glucose metabolism disorders, and cannot meet the needs of patients who avoid sugar intake such as diabetes, obesity, and hyperlipidemia. Therefore, sugar-free compound honeysuckle granules have appeared on the market according to demand. For example, the patent application with application number 201611145436.5 records a sucrose-free compound honeysuckle granules and a preparation method thereof, which are made of 450-550 parts of honeysuckle, 450-550 parts of forsythia, 150-180 parts of scutellaria, 2-4 parts of aspartame, and 4-6 parts of dextrin. However, since the sweetener aspartame is not acceptable to patients with phenylketonuria, its dissolution rate will be slow if the water temperature is lower than 70 degrees Celsius during brewing. On the other hand, in the process of processing the thick drug extract into granules in the prior art, some temperature-sensitive and volatile active ingredients in the raw materials are easily destroyed, thereby affecting the shelf life of the traditional Chinese medicine preparation and reducing the clinical efficacy. Summary of the invention

[0003] In view of the above technical problems, the technical solution of the present invention provides a method for preparing a sugar-free compound honeysuckle granule, comprising the steps of preparing a honeysuckle distilled extract, preparing a honeysuckle extract, preparing a scutellaria baicalensis and forsythia extract, and a granulation step, wherein the granulation step specifically comprises the following steps:

[0004] Weighing excipients according to 0.8-3.6 times the total mass of the honeysuckle distilled extract, honeysuckle extract and scutellaria baicalensis and forsythia extract, weighing stevioside according to 0.43-0.45% of the total mass of the honeysuckle distilled extract, honeysuckle extract and scutellaria baicalensis and forsythia extract, wherein the excipients include one or more of dextrin, sodium carboxymethyl cellulose and mannitol;

[0005] Mixing the honeysuckle distilled extract, honeysuckle extract, scutellaria baicalensis and forsythia extract, the excipients and the stevioside to prepare wet granules;

[0006] The wet granules are dried, granulated and then packaged to obtain finished sugar-free compound honeysuckle granules.

[0007] Correspondingly, the technical solution of the present invention also proposes sugar-free compound honeysuckle granules prepared by the above method.

[0008] The technical scheme of the present invention provides a method for preparing sugar-free compound honeysuckle granules. The sugar-free honeysuckle granules prepared by the method have good solubility at low temperatures, high content of active ingredients, and retain the unique fragrance of honeysuckle to a certain extent, which is conducive to being accepted by a wider patient group. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 :Production steps of some solutions;

[0010] Figure 2 :Production steps of some solutions;

[0011] Figure 3 :Process flow charts of some schemes;

[0012] Figure 4 :Process flow charts of some schemes. DETAILED DESCRIPTION

[0013] The following examples further illustrate the content of the present invention, but should not be construed as limiting the present invention. Without departing from the spirit and substance of the present invention, modifications or substitutions made to the methods, steps or conditions of the present invention all fall within the scope of the present invention.

[0014] It should be noted that the honeysuckle in the present invention is a dried product or fresh product (the shelf life of the fresh product is preferably within 36 hours after picking) of the buds or flowers to be opened of the honeysuckle plant Lonicera japonica Thunb. of the Caprifoliaceae family, which can clear away heat and detoxify. It can treat fever caused by febrile diseases, dysentery caused by heat toxins, carbuncles, swelling and toxins, scrofula, and hemorrhoid fistula. The scutellaria baicalensis in the following scheme is the dried root of Scutellaria baicalensis Georgi of the genus Scutellaria of the Lamiaceae family. The Compendium of Materia Medica records that scutellaria baicalensis tastes bitter, is flat in nature, and is non-toxic; it mainly treats various heat, yellow pox, edema, malignant sores, fire ulcers and other diseases. The forsythia in the following scheme is the dried fruit of the forsythia suspensa (Thunb.) Vahl of the Oleaceae family, which mainly treats warm heat, erysipelas, macules, carbuncles, swelling and toxins, scrofula, and urinary retention.

[0015] Sweeteners with high sweetness and low calories can reduce the addition of sucrose while maintaining the sweetness of the product. First of all, sweeteners can be divided into natural sweeteners and artificial sweeteners according to their sources. Natural sweeteners include xylitol, stevioside, and mogroside, and artificial sweeteners include saccharin sodium, aspartame, acesulfame potassium, and neotame. By comparing several natural and artificial sweeteners, it is studied that changing the auxiliary materials of compound honeysuckle granules can replace the flavor correction function with stevioside.

[0016] While examining the existing technologies, a comprehensive screening of various pharmaceutically acceptable sweeteners was first conducted, and the screening results are shown in Table 1-2.

[0017] Table 1. Common sweetener types

[0018]

[0019] Table 2. Comparison of properties of common sweeteners

[0020]

[0021]

[0022] According to the investigation results in Table 1-2, since stevioside is a glycoside extracted from the leaves of the natural plant Stevia, it is a natural energy-free high-sweetness sweetener with high safety, low toxicity and side effects, and good heat resistance and stability. In addition, stevioside not only does not cause dental caries, but toxicological experiments show that it does not have teratogenic, carcinogenic, and mutagenic toxicity, and can also lower blood pressure and blood sugar. Compared with other sweeteners, stevioside is safe to eat and is an ideal sweetener that can replace sucrose. It is planned to use a smaller amount of stevioside as a flavoring agent.

[0023] The following examples, based on the proposed stevioside as a sweetener, continue to investigate the mixing of fillers with it as an auxiliary material to replace sucrose.

[0024] Experimental Example 1 Investigation of the Granulation Process of Compound Honeysuckle Granules

[0025] This test example was carried out according to the prescription amount of 375±5g of honeysuckle, 375±5g of forsythia, 125±5g of scutellaria, and appropriate amount of pharmaceutical excipients. Figure 1 The steps shown in:

[0026] S1 step of preparing honeysuckle distilled extract;

[0027] S2 is a step of preparing a honeysuckle extract;

[0028] S3 is a step for preparing a scutellaria baicalensis and forsythia extract;

[0029] S4 granulation step.

[0030] exist Figure 1 Based on the steps of, the steps of preparing the honeysuckle distilled extract in this test example include:

[0031] S11 weigh 3 parts by mass of honeysuckle;

[0032] S12: putting the weighed honeysuckle into an extraction tank, using water 4 times the volume of the honeysuckle to distill it, and after boiling, controlling the temperature to 90-100 degrees Celsius to collect the distillate, and filtering the distillate to obtain the honeysuckle distilled extract.

[0033] In this test example, the steps of preparing honeysuckle extract include:

[0034] After adding 5-6 times the volume of water into the distilled honeysuckle residue and boiling for 0.5 hour, the honeysuckle extract is collected, and the honeysuckle extract is concentrated to a relative density of 1.15-1.18 times to obtain the honeysuckle primary extract, and the honeysuckle primary extract is extracted with at least 3 volumes of 95% ethanol, and the ethanol extract is collected. After recovering the ethanol, the remaining medicinal liquid is concentrated to a relative density of 1.30-1.35 times to obtain the honeysuckle extract.

[0035] Specifically, the steps of preparing the Forsythia and Scutellaria extract in this test example include:

[0036] S31 Weigh 3 parts by weight of Forsythia suspensa and 1 part by weight of Scutellaria baicalensis;

[0037] S32: boiling the forsythia and scutellaria twice, adding 6 times the volume of water each time, boiling for 1 hour each time, combining the two extracts and filtering, and concentrating the filtrate to a relative density of 1.15-1.18 times, thereby obtaining the forsythia and scutellaria primary extract;

[0038] S33 extracts the Fructus Forsythiae and Scutellariae baicalensis extract with ethanol, collects the supernatant after extraction and recovers the ethanol therein, and concentrates the remaining medicinal liquid to a relative density of 1.30-1.35 times to obtain the Fructus Forsythiae and Scutellariae baicalensis extract.

[0039] The honeysuckle distilled extract, honeysuckle extract, and the total extract of the scutellaria baicalensis and forsythia extract were divided into four portions, 1 / 5 of each batch, and each portion was added with a combination of stevioside and dextrin, soluble starch, microcrystalline cellulose (MCC), and sodium carboxymethyl cellulose (CMC-Na) according to the designed proportions in Table 3 below. Soft material was made with ethanol, granulated with a 16-mesh sieve, the formability of the granulation process was observed, the wet granules were dried at 80°C, granulated, and mixed.

[0040] In the granulation step of this test example, it was found that since there are many types of pharmaceutically acceptable granule excipients, such as soluble starch, sodium carboxymethyl cellulose (CMC-Na), dextrin, microcrystalline cellulose (MCC), etc., according to the product characteristics and the characteristics of different excipients, the excipients that are conducive to the dissolution of the granules, strong moisture resistance, good flow-aiding effect, and the dosage meet the requirements of the original dosage form, while meeting the original number of times and dosage, are selected according to the formability, solubility, angle of repose, and moisture content of the granules made after the excipients are mixed with the extract and the distillate. This test example selects stevioside and one of dextrin, soluble starch, microcrystalline cellulose (MCC), sodium carboxymethyl cellulose (CMC-Na) as excipients for screening experiments.

[0041] The dosage of auxiliary materials of stevioside in combination with dextrin, soluble starch, microcrystalline cellulose (MCC) and sodium carboxymethyl cellulose (CMC-Na) to replace sucrose was investigated according to the process ratio. Taking into account the physical properties of stevioside and its flavor correction function, a small dose of 1g of stevioside was set for the granulation step, and the granulation effect was compared.

[0042] Table 3. Test of excipients in compound honeysuckle granules

[0043]

[0044]

[0045] After investigation of Test Example 1, it was found that the combination of stevioside and soluble starch as auxiliary materials has the expected output and good molding rate, and the appearance and particle size are uniform. The preparation of stevioside combined with dextrin and microcrystalline cellulose (MCC) is smoother and easier. Stevioside and sodium carboxymethyl cellulose (CMC-Na) are slightly sticky, granulation is difficult, and it is easy to stick and agglomerate when drying, and the output rate is poor. When the auxiliary materials stevioside and sodium carboxymethyl cellulose (CMC-Na) are matched, it is not easy to pass through the sieve, and large particles remain on the sieve, which is brown and uneven in color; when the auxiliary materials are stevioside and soluble starch, it is easy to pass through the sieve, fibrous, brown, but there are more fine powders, and the particles are uniform in color and dissolved in water in a suspended state.

[0046] Based on Test Example 1 and previous investigations, the technical solutions and effects of the present invention are further illustrated by the following embodiments and test examples.

[0047] Example 1

[0048] The preparation method of the sugar-free compound honeysuckle granules of Example 1 is carried out as follows according to the prescription of 375±5g honeysuckle, 375±5g forsythia, 125±5g scutellaria, 160±5g dextrin, and 1.5±0.1g stevioside. Figure 1 The following steps:

[0049] S1 step of preparing honeysuckle distilled extract;

[0050] S2 is a step of preparing a honeysuckle extract;

[0051] S3 is a step for preparing the scutellaria baicalensis and forsythia extract;

[0052] S4 granulation step.

[0053] The difference from Experimental Example 1 is that in the granulation step of this embodiment: weigh dextrin that is 3.6 times the total mass of the honeysuckle distilled extract, honeysuckle extract and the scutellaria baicalensis and forsythia extract, mix the weighed dextrin with the honeysuckle extract, forsythia suspensa and scutellaria baicalensis extract, honeysuckle distilled extract and stevioside, add ethanol at 95% of the volume of the mixture, stir and break to make a uniform soft material, transfer the prepared soft material to a 15-20 mesh nylon screen swing granulator to make type A wet granules.

[0054] The wet particles of type A are dried in a dryer by hot air drying at an air supply temperature of 80° C. for 20 minutes.

[0055] The dried granules are sized and packaged to obtain the finished sugar-free compound honeysuckle granules.

[0056] Embodiment 2 (most preferred scheme)

[0057] The preparation method of the sugar-free compound honeysuckle granules of Example 2 is as follows: honeysuckle 420-425g (fresh), forsythia suspensa 375±5g, scutellaria 125±5g, sodium carboxymethyl cellulose 160g, mannitol 45.5g stevioside 1.5g, Figure 1 Steps S1-4 in .

[0058] However, unlike the previous scheme, in the granulation step of Example 2, Figure 2 : Weigh 0.8 times the mass of mannitol and 2.8 times the mass of sodium carboxymethyl cellulose of the total mass of the honeysuckle distilled extract, honeysuckle extract and the scutellaria baicalensis and forsythia extract, add the weighed mannitol, sodium carboxymethyl cellulose CMC-Na and stevioside to the honeysuckle distilled extract, add appropriate amount of distilled water to mix and dissolve, then add the honeysuckle extract and forsythia scutellaria extract to mix, add 95% by volume of ethanol, stir and break to make a uniform soft material, transfer the prepared soft material to a 20-mesh nylon screen swing granulator to make type B wet granules.

[0059] The wet particles of type B are dried under vacuum and low temperature conditions; sublimation drying is performed at a vacuum temperature of -15 degrees Celsius for 16 hours.

[0060] The granules prepared in Example 2 have a light yellow appearance, are sweet, slightly bitter, and have a light floral aroma.

[0061] Other optional embodiments based on Example 2 are to perform sublimation drying at a temperature of -20 degrees Celsius under vacuum conditions for 12 hours, or to make appropriate adjustments based on the conditions of Example 2.

[0062] Example 3

[0063] According to the prescription of 375g honeysuckle, 375g forsythia, 125g scutellaria, 170g dextrin, and 1.5g stevioside, proceed as follows: Figure 3-4 The following steps:

[0064] (1) Weighing: According to the above prescription, weigh the Chinese herbal medicine pieces of honeysuckle, forsythia, and scutellaria, respectively, and check them, clear the area, and proceed to the next process.

[0065] (2) Honeysuckle distillate: Put the weighed honeysuckle into an extraction tank for distillation, add 4 times the amount of water, control the temperature at 90℃~100℃ after boiling, collect 720ml (±10ml) of distillate, filter the distillate, and store it in another container for later use.

[0066] (3) Honeysuckle extract: Add 6 times the amount of water to the residue and boil for 30 minutes. Filter the extract and combine it with the filtrate after distillation and put it into a liquid storage tank for concentration.

[0067] (4) Concentration: The above-mentioned liquid medicine is pumped into a double-effect concentrator and concentrated into an extract with a relative density of 1.15-1.18 (measured at 80°C).

[0068] (5) Alcohol precipitation: Add the concentrated extract into the alcohol precipitation tank, turn on the stirring paddle, and slowly add 3 times the volume of 95% alcohol into the tank while stirring. When adding ethanol, follow the principle of slowly increasing the amount of stirring and increasing it step by step to prevent the occurrence of "wrapping". After adding ethanol, continue stirring for 30 minutes to mix the liquid evenly, let it stand for 24 hours, and filter.

[0069] (6) Concentration and cream collection: The supernatant is pumped into a double-effect concentrator to recover ethanol until the liquid medicine has no alcohol taste. The recovered ethanol is pumped into an alcohol storage tank to concentrate the liquid medicine to an extract with a relative density of 1.30-1.35 (thermal measurement at 60-65°C), and then pumped into a cream collection room through a pipeline for cream collection and packaging.

[0070] (7) Extraction of Forsythia suspensa and Scutellaria baicalensis: weigh the clean medicinal materials of Scutellaria baicalensis and Forsythia suspensa into an extraction tank for extraction. The extraction is decocted twice, and 6 times the amount of water is added each time. The decocted each time for 1 hour. The two extracts are combined and filtered, and the filtrate is poured into a liquid medicine storage tank for concentration.

[0071] (8) Concentration: The extract is pumped into a double-effect concentrator to concentrate the liquid into an extract with a viscosity of 1.15-1.18 (80°C).

[0072] (9) Alcohol precipitation: Add the concentrated extract into the alcohol precipitation tank, turn on the stirring paddle, and slowly add 3 times the amount of 95% ethanol into the tank while stirring. When adding ethanol, follow the principle of slowly increasing the amount of stirring and increasing it step by step to prevent the occurrence of "wrapping". After adding ethanol, continue stirring for 30 minutes to mix the medicine solution evenly, let it stand for 24 hours, and filter.

[0073] (10) Concentration and collection of cream: The supernatant is pumped into a double-effect concentrator to recover ethanol until the liquid medicine has no alcohol taste. After the alcohol is collected, the liquid medicine is concentrated. The relative density of the concentrated extract should be 1.30-1.35 (thermal measurement at 60-65℃). It is pumped into the cream collection room through a pipeline for collection and packaging.

[0074] (11) Weighing ingredients: The technician in the preparation workshop checks whether the raw and auxiliary materials used are consistent with the batch production instructions and signs on the records. The corresponding materials are weighed according to the theoretical amount in the batch production instructions.

[0075] (12) Granulation: Add the weighed and verified dextrin into a high-speed mixing granulator, add the weighed and verified honeysuckle extract, forsythia and scutellaria extract, honeysuckle distillate, and stevioside in sequence, add 95% by volume ethanol, stir and chop for 40-80 seconds to make a uniform soft material. Install a 16-mesh nylon screen according to the process requirements, and add the prepared soft material into a swing granulator with a stainless steel material scoop to make granules.

[0076] (13) Drying: Pour the prepared wet granules into the dryer, start the equipment operation system, and start the drying operation. During the drying process, the air supply temperature is 80°C (temperature difference range ±5°C); the drying time is 20 minutes. The dried granules are transferred to the granulation process for granulation operation.

[0077] (14) Granulation: When granulating, the mesh size of the upper sieve is 10 mesh (No. 1 sieve), and the mesh size of the lower sieve is 80 mesh (No. 5 sieve).

[0078] (15) Total mixing: Set the mixing time to 20 minutes to ensure that the particles are evenly mixed and discharged. After total mixing, the particles are packed into clean bags.

[0079] (16) Granule packaging: Adjust the longitudinal and transverse sealing temperatures between 100°C and 180°C, and pack 4 grams per bag.

[0080] The granules prepared in Example 3 are light yellow to yellow-brown in color and taste sweet and slightly bitter.

[0081] Test Example 2

[0082] Test samples: 16 batches of granules prepared in Test Example 1, 50 g / batch, were divided into four groups according to the composition of auxiliary materials, and 200 g of granules prepared in Example 2 were evenly divided into 4 batches, and several tests were carried out on each batch of 50 g.

[0083] Test method: Test fluidity, solubility, dissolution rate, moisture content and other indicators according to the 0104 granule test method of Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0084] (1) Liquidity test

[0085] The angle of repose determination method was adopted, and the solid funnel method was applied. Three funnels were connected in series and fixed on a horizontally placed coordinate paper at a height of about 1 cm. The powders made with different excipients were carefully poured into the funnel along the wall of the funnel until the tip of the powder cone formed on the coordinate paper touched the bottom of the funnel. The diameter of the cone bottom (2R) was measured by the coordinate paper, and the angle of repose (tanα=H / R) was calculated. The test was repeated five times and the average was taken. The experimental results are shown in the following table.

[0086] Table 4. Flowability test (angle of repose)

[0087]

[0088] The smaller the angle of repose, the smaller the friction and the better the fluidity. It is generally believed that the fluidity is good when θ≤30°, and the fluidity requirements in the production process can be met when θ≤40°. The above samples all meet the requirements.

[0089] (2) Determination of particle size

[0090] Take 30g of the test sample after drying, weigh it, put it in 10-mesh and 80-mesh sieves, keep it horizontal and sieve it back and forth, tap it while sieving for 3 minutes. Take the particles and powder that cannot pass through the 10-mesh sieve and can pass through the 80-mesh sieve, weigh it, and calculate the percentage (%).

[0091] Table 5. Particle size and particle size distribution measurement results (distribution percentage)

[0092]

[0093]

[0094] According to the particle size and particle size distribution determination method (General Rule 0982 Method 2 Screening Method), the sum of particles that do not pass through the No. 1 sieve and those that can pass through the No. 5 sieve shall not exceed 15%. The particles of the above-mentioned test batches all meet the requirements.

[0095] (3) Determination of moisture

[0096] According to the provisions of 0832 (Method 2 Drying Method) of the General Rules of Part IV of the 2020 Edition of the Chinese Pharmacopoeia, weigh 2.0g of granules, spread them flat in a flat weighing bottle that has been dried to constant weight, with a thickness of no more than 5mm, accurately weigh, open the bottle cap and dry it in a constant temperature drying oven at 105℃ for 5 hours, cover the bottle cap, place it in a desiccator, cool it for 0.5h, accurately weigh it, dry it at the above temperature for 1h, cool it, and weigh it until the difference in weight does not exceed 5mg for two consecutive times. Calculate the water content (%) in the test sample based on the lost weight.

[0097] Table 6. Water content test results (%)

[0098]

[0099] Chinese herbal medicine granules shall be measured according to the moisture determination method (General Rule 0832). Unless otherwise specified, the moisture content shall not exceed 8.0%. The above-mentioned test batches all meet the requirements.

[0100] (4) Determination of solubility

[0101] According to the 2020 edition of the Chinese Pharmacopoeia (General Chapter 0104) for the inspection of soluble particles in granules, 10g of each sample was accurately weighed, 200ml of hot water (90 degrees Celsius) was added, stirred for 5 minutes, and the dissolution state was observed. In the hot water, the combination of stevioside with dextrin, soluble starch, and sodium carboxymethyl cellulose (CMC-Na) was completely dissolved, which met the requirements; microcrystalline cellulose (MCC) was partially insoluble in water and easily precipitated, which did not meet the requirements.

[0102] Table 7. Melting state in hot water

[0103]

[0104] Next, we will continue to examine the solubility in room temperature water. Weigh 10g of each of the above samples accurately, add 200ml of distilled water at 25 degrees Celsius, stir for 5 minutes, and observe the dissolution state. In the above samples, the granules of dextrin and soluble starch were not completely dissolved in distilled water at room temperature. Sodium carboxymethyl cellulose (CMC-Na) and the combination of sodium carboxymethyl cellulose (CMC-Na) and mannitol were all dissolved. Microcrystalline cellulose (MCC) is partially insoluble in water.

[0105] Table 8. Melting state at room temperature

[0106]

[0107]

[0108] This experiment confirmed that dextrin and soluble starch need hot water to dissolve in order to obtain a more ideal dissolution rate, especially the soluble starch has a slower dissolution rate.

[0109] (5) Determination of dissolution rate

[0110] Take a glass centrifuge tube that has been dried to constant weight, weigh 0.5g of particles, add 10mL of boiling water, stir and shake for 5 minutes, centrifuge at 3000r / min for 15 minutes, discard the supernatant, dry the residue at 80℃ to constant weight, and weigh accurately. Dissolution rate = (total particle weight - undissolved particle weight) / total particle weight * 100%. The dissolution rate test results are shown in the following table.

[0111] Table 5. Melting rate measurement results

[0112] excipient 1 2 3 4 Soluble starch 92.13 91.88 90.99 92.54 Microcrystalline Cellulose 55.86 54.57 56.13 54.90 Sodium Carboxymethyl Cellulose 94.20 95.03 95.16 95.46 dextrin 93.17 93.95 93.45 93.50 CMC-Na+Mannitol 96.12 96.04 95.95 96.20

[0113] The solubility of stevioside with dextrin and sodium carboxymethyl cellulose (CMC-Na) was better, that with soluble starch was second, and that with microcrystalline cellulose (MCC) was the best.

[0114] Based on a comprehensive analysis of particle size qualification rate, angle of repose, moisture, solubility, granulation and molding rate, stevioside is selected as a sweetener to replace auxiliary material sucrose, and dextrin or CMC-Na + mannitol can be selected as excipients for industrial production.

[0115] Comparative Example 1

[0116] The same recipe as in Example 2 was used, except that the granulation was performed under the hot air drying conditions as in Example 1. The amount of fine granules obtained was significantly increased.

[0117] (4) Solubility determination was carried out according to the method of Test Example 2. 200 ml of distilled water at room temperature of 25 degrees Celsius was stirred for 5 minutes, and the dissolution state was observed. A small amount of suspended particles was found.

[0118] Comparative Example 2

[0119] According to the prescription of Example 2, according to the granulation method disclosed in the patent application with application number 201611145436.5, sucrose-free compound honeysuckle granules are prepared. The obtained honeysuckle distillate, honeysuckle extract and the obtained forsythia and scutellaria thick paste are mixed evenly to obtain a mixture, and 0.5-1.5 times the weight of the above mixture with a mass concentration of 40-60% ethanol is added, and stirred evenly to obtain a mixed thick paste; 4-6 parts by weight of dextrin and 2-4 parts by weight of aspartame are mixed evenly, added to the above mixed thick paste, mixed evenly, and soft materials are obtained, granulated, dried, granulated, and packaged to obtain the sucrose-free compound honeysuckle granules.

[0120] (2) Particle size was measured according to the method of Test Example 2, and it was found that the particles did not meet the requirements of the Pharmacopoeia.

[0121] Based on the above embodiments and test examples, it can be concluded that changing the "powdered sugar" to "dextrin and stevioside" or "sodium carboxymethyl cellulose (CMC-Na) and mannitol and stevioside" in the compound honeysuckle granules is reasonable and feasible, and suitable for industrial production.

[0122] Although the present invention has been described in detail above by general description, specific implementation methods and experiments, it is obvious to those skilled in the art that some modifications or improvements can be made to the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all belong to the scope of protection claimed by the present invention.

Claims

1. A method for preparing sugar-free compound honeysuckle granules, characterized in that: The method comprises the steps of preparing a honeysuckle distilled extract, preparing a honeysuckle extract, preparing a scutellaria baicalensis and forsythia suspensa extract and a granulation step, wherein the granulation step specifically comprises the following steps: Weighing excipients according to 0.8-3.6 times the total mass of the honeysuckle distilled extract, honeysuckle extract and scutellaria baicalensis and forsythia extract, weighing stevioside according to 0.43-0.45% of the total mass of the honeysuckle distilled extract, honeysuckle extract and scutellaria baicalensis and forsythia extract, wherein the excipients include one or more of dextrin, sodium carboxymethyl cellulose and mannitol; Mixing the honeysuckle distilled extract, honeysuckle extract, scutellaria baicalensis and forsythia extract, the excipients and the stevioside to prepare wet granules; The wet granules are dried, granulated and then packaged to obtain finished sugar-free compound honeysuckle granules.

2. The method for preparing the sugar-free compound honeysuckle granules according to claim 1, characterized in that: The granulation step specifically includes: weighing dextrin of 3-3.6 times the total mass of the honeysuckle distilled extract, honeysuckle extract and the scutellaria baicalensis and forsythia extract, mixing the weighed dextrin with the honeysuckle extract, forsythia suspensa and scutellaria baicalensis extract, honeysuckle distilled extract and stevioside, adding ethanol according to 95% of the volume of the mixture, stirring and breaking to make a uniform soft material, transferring the prepared soft material to a 15-20 mesh nylon screen swing granulator to make type A wet granules.

3. The method for preparing the sugar-free compound honeysuckle granules according to claim 2, characterized in that: In the granulation step, the wet granules of type A are dried in a dryer at an air supply temperature of 80° C. for 20 minutes.

4. The method for preparing the sugar-free compound honeysuckle granules according to claim 1, characterized in that: The granulation step specifically includes: weighing 0.8 times the mass of mannitol and 2.8-3 times the mass of sodium carboxymethyl cellulose of the total mass of the honeysuckle distilled extract, the honeysuckle extract and the scutellaria baicalensis and forsythia extract, adding the weighed mannitol, sodium carboxymethyl cellulose and stevioside to the honeysuckle distilled extract, adding an appropriate amount of distilled water to mix and dissolve, then adding the honeysuckle extract and the forsythia scutellaria extract to mix evenly, adding 95% by volume of ethanol, stirring and breaking to make a uniform soft material, transferring the prepared soft material to a 20-mesh nylon screen swing granulator to make type B wet granules.

5. The method for preparing the sugar-free compound honeysuckle granules according to claim 4, characterized in that: The wet particles of type B are dried under vacuum and low temperature conditions; preferably, the vacuum conditions are sublimation drying at a temperature of -20 to -10 degrees Celsius for 12 to 18 hours.

6. The method for preparing the sugar-free compound honeysuckle granules according to claim 1, characterized in that: The steps of preparing the honeysuckle distilled extract include: Weigh 3 parts by mass of honeysuckle, The weighed honeysuckle is put into an extraction tank, and distilled with water 4 times the volume of the honeysuckle. After boiling, the temperature is controlled at 90-100 degrees Celsius to collect the distillate, and the distillate is filtered to obtain the honeysuckle distilled extract.

7. The method for preparing the sugar-free compound honeysuckle granules according to claim 6, characterized in that: The step of preparing honeysuckle extract comprises: After adding 5-6 times the volume of water into the distilled honeysuckle residue and boiling for 0.5 hour, the honeysuckle extract is collected, and the honeysuckle extract is concentrated to a relative density of 1.15-1.18 times to obtain the honeysuckle primary extract, and the honeysuckle primary extract is extracted with at least 3 volumes of 95% ethanol, and the ethanol extract is collected. After recovering the ethanol, the remaining medicinal liquid is concentrated to a relative density of 1.30-1.35 times to obtain the honeysuckle extract.

8. The method for preparing the sugar-free compound honeysuckle granules according to claim 1, characterized in that: The honeysuckle is a fresh honeysuckle flower medicinal material.

9. The method for preparing the sugar-free compound honeysuckle granules according to claim 1, characterized in that: The steps of preparing the Fructus Forsythiae and Scutellariae Radix extract include: Weigh 3 parts by weight of Forsythia suspensa and 1 part by weight of Scutellaria baicalensis; The forsythia and scutellaria are decocted twice, 6 times the volume of water is added each time, and the decocting is performed for 1 hour each time, the two extracts are combined and filtered, and the filtrate is concentrated to a relative density of 1.15-1.18 times to obtain the forsythia and scutellaria primary extract; The forsythia and scutellaria primary extract is extracted with ethanol, the supernatant after extraction is collected and the ethanol therein is recovered, and the remaining medicinal liquid is concentrated to a relative density of 1.30-1.35 times to obtain the forsythia and scutellaria extract.

10. Sugar-free compound honeysuckle granules prepared according to any one of the methods described in claims 1-9.

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