Rheum officinale formula granules and preparation method thereof

Abstract

The invention belongs to the technical field of pharmacy, and particularly relates to rhubarb formula granules and a preparation method thereof.The preparation method comprises the following steps that rhubarb medicinal materials are soaked in normal-temperature water and cut into thick pieces, and rhubarb decoction pieces are prepared; adding water of which the mass is 6-10 times that of the yellow decoction pieces, carrying out warm soaking at 65-95 DEG C for 5-30 minutes, and filtering to obtain first filtrate and first filter residues; adding water which is 16-24 times of the mass of the yellow decoction pieces into the first filter residues, decocting, and filtering to obtain second filtrate and second filter residues; adding the second filter residue into water which is 6-14 times of the mass of the Huang decoction piece, decocting, and filtering to obtain a third filtrate and a third filter residue; combining the first filtrate, the second filtrate and the third filtrate, and concentrating under reduced pressure to obtain flow paste; and drying and crushing the fluid paste, adding or not adding auxiliary materials into the fluid paste, and granulating to obtain the rhubarb formula granules. The preparation method is simple in step, low in energy consumption and smooth in production process, and the rhubarb formula granules are good in quality, stable in yield and suitable for industrial large-scale production.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceuticals, and in particular relates to rhubarb formula granules and a preparation method thereof. Background Art

[0002] Rhubarb is the dried root and rhizome of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. of the Polygonaceae family. It is included in the 2020 edition of the Chinese Pharmacopoeia and was first recorded in the Shennong's Herbal Classic. As a commonly used Chinese medicine, rhubarb occupies an important position in botanical purgatives. It has the effects of purgation, clearing away heat and purging fire, cooling blood and detoxifying, removing blood stasis and dredging menstruation, and removing dampness and jaundice. It can be used for constipation caused by excess heat, vomiting and bleeding due to blood heat, red eyes and swollen throat, carbuncle, abdominal pain due to intestinal carbuncle, amenorrhea due to blood stasis, postpartum blood stasis, traumatic injury, damp-heat dysentery, jaundice and red urine, stranguria, edema; external treatment of burns and scalds. The chemical composition of rhubarb is complex. Modern research shows that the effective ingredients of rhubarb include bound and free anthraquinones / anthrones, diphenylethylenes, butyrophenones, chromones, flavonoids, etc.

[0003] Chinese medicine formula granules are made from single medicinal materials, processed into Chinese medicine slices, and then extracted, concentrated, dried, and granulated. After the clinical prescription of traditional Chinese medicine, they are used by patients. The quality level of Chinese medicine formula granules is evaluated by the consistency of the three major indicators of paste yield, fingerprint or characteristic spectrum, and main active ingredient transfer rate (or content) with the standard decoction (prepared by the traditional Chinese medicine decoction preparation method).

[0004] The existing production technology of rhubarb formula granules mainly adopts the static decoction extraction method, but rhubarb contains more mucilage and is easy to gelatinize during decoction. At present, there are defects such as long liquid transfer time, too high yield, more active ingredient loss, unsmooth production, and low efficiency. In addition, the main active ingredients of rhubarb, such as free anthraquinone, are poorly water-soluble and thermally unstable, which will lead to low component transfer rate, content deviating from the technical requirements of standard decoctions, and large batch differences, which will cause a huge waste of resources, seriously affect product quality, and affect the safety and effectiveness of clinical medication; and the existing regulations stipulate that the solvent used for formula granule extraction is pharmaceutical water. However, in the existing research on the preparation process of rhubarb formula granules, there is often only a simple preparation process, and there is no report on the research on key processes that affect quality such as production smoothness. In addition, the solvents are mostly non-pharmaceutical water. For example, in the patent with application number 201711432302.6, hot water is directly added to the rhubarb for decoction, and the decoction is performed once; in the patent with application number 201510018121.3, ethanol is used for extraction; and the patent with application number 201911020852.6 also uses an alcohol extraction process. Summary of the invention

[0005] Therefore, the technical problem to be solved by the present invention is to overcome the defects of the prior art in preparing rhubarb formula granules, such as low anthraquinone transfer rate, especially low free anthraquinone transfer rate, large loss of active ingredients, uneven production, low efficiency and poor product quality, thereby providing rhubarb formula granules and a preparation method thereof.

[0006] To this end, the present invention provides the following technical solutions.

[0007] The invention provides a preparation method of rhubarb formula granules, comprising the following steps: S1: soaking rhubarb medicinal materials in water at room temperature, cutting thick slices to obtain rhubarb decoction slices; S2: taking the rhubarb decoction slices, adding water 6 to 10 times the mass of the rhubarb decoction slices and soaking at 65 to 95°C for 5 to 30 minutes, filtering to obtain a first filtrate and a first filter residue; S3: boiling the first filter residue with water 16 to 24 times the mass of the rhubarb decoction slices, filtering to obtain a second filtrate and a second filter residue; S4: boiling the second filter residue with water 6 to 14 times the mass of the rhubarb decoction slices, filtering to obtain a third filtrate and a third filter residue; S5: combining the first filtrate, the second filtrate and the third filtrate, concentrating under reduced pressure to obtain a fluid paste; S6: drying the fluid paste, crushing it, adding or not adding auxiliary materials thereto, granulating it, and obtaining rhubarb formula granules.

[0008] It is well known in the art that in common Chinese herbal medicine slices, the thickness of thick slices is 2 to 4 mm.

[0009] Optionally, in S1, the rhubarb medicinal material is soaked in normal temperature water with a volume of 1 to 8 times the mass of the rhubarb medicinal material for 4 to 12 hours.

[0010] Optionally, in S3, the decocting time is 5 to 30 minutes and the temperature is 98 to 100°C.

[0011] Optionally, in S4, the decocting time is 5 to 30 minutes and the temperature is 98 to 100°C.

[0012] Optionally, in S5, the temperature of the reduced pressure concentration is 50 to 80° C.; typically, but not limiting, the vacuum degree range used for the reduced pressure concentration is -0.08 to -0.04 MPa.

[0013] Optionally, in S6, the pulverizing is to pulverize the dried fluid paste to a particle size of ≤100 mesh. Typically, but not limited to, this purpose can be achieved by passing the dried fluid paste through a 100 mesh screen.

[0014] Optionally, in S5, the relative density of the obtained fluid paste is 1.01 to 1.12 g / mL.

[0015] Optionally, the preparation method comprises the following steps: S1: soaking rhubarb medicinal materials in room temperature water of 1 to 3 times the mass of rhubarb medicinal materials for 4 to 8 hours, cutting into thick slices, and preparing rhubarb decoction slices; S2: taking rhubarb decoction slices, adding water of 8 to 10 times the mass of rhubarb decoction slices and soaking at 80 to 95°C for 5 to 15 minutes, filtering to obtain a first filtrate and a first filter residue; S3: boiling the first filter residue with water of 20 to 24 times the mass of rhubarb decoction slices at 100°C for 5 to 15 minutes, filtering to obtain a second filtrate and a second filter residue; S4: boiling the second filter residue with water of 10 to 14 times the mass of rhubarb decoction slices at 100°C for 5 to 15 minutes, filtering to obtain a third filtrate and a third filter residue; S5: combining the first filtrate, the second filtrate, and the third filtrate, concentrating under reduced pressure to obtain a fluid paste; S6: drying the fluid paste, crushing it, adding or not adding auxiliary materials thereto, granulating it, and obtaining rhubarb formula granules.

[0016] Optionally, the auxiliary material includes at least one of dextrin, maltodextrin, β-cyclodextrin, lactose, silicon dioxide, and magnesium stearate. Typically, but not limited to, the auxiliary materials mainly used in the production process are dextrin, maltodextrin, β-cyclodextrin, and lactose; silicon dioxide and magnesium stearate are used in small amounts, usually about 0.2% of the extract, to improve the granulation effect.

[0017] Optionally, the amount of the auxiliary material added is 0% to 11% of the mass of the rhubarb formula granules.

[0018] Optionally, in S6, the granulation method includes any one of dry granulation, wet granulation, and one-step granulation.

[0019] Optionally, in S6, the drying method includes spray drying; typically but not limitingly, the inlet air temperature of the spray drying is 160-210°C, and the outlet air temperature is 85-120°C.

[0020] The present invention also provides rhubarb formula granules prepared by the preparation method.

[0021] The beneficial effects of the present invention are:

[0022] The preparation method of rhubarb formula granules provided by the present invention comprises the following steps: S1: soaking rhubarb medicinal materials in water at room temperature, cutting thick slices, and preparing rhubarb decoction slices; S2: taking rhubarb decoction slices, adding water 6 to 10 times the mass of rhubarb decoction slices and soaking at 65 to 95°C for 5 to 30 minutes, filtering, and obtaining a first filtrate and a first filter residue; S3: boiling the first filter residue with water 16 to 24 times the mass of rhubarb decoction slices, filtering, and obtaining a second filtrate and a second filter residue; S4: boiling the second filter residue with water 6 to 14 times the mass of rhubarb decoction slices, filtering, and obtaining a third filtrate and a third filter residue; S5: combining the first filtrate, the second filtrate, and the third filtrate, and concentrating under reduced pressure to obtain a flow paste; S6: drying and crushing the flow paste, adding or not adding auxiliary materials thereto, and granulating to obtain rhubarb formula granules. The preparation method has simple steps, low energy consumption, short time, smooth production process, good quality of rhubarb formula granules, stable yield, and can be applied to industrial large-scale production. The prepared rhubarb formula granules have high free anthraquinone and total anthraquinone contents and content transfer rates, retaining the anthraquinone content in rhubarb to the greatest extent, thereby ensuring the quality of the rhubarb formula granules to a greater extent and making them meet the national drug standards for rhubarb formula granules.

[0023] In this preparation method, there is no need to use organic solvents to extract the drug, so that the quality and safety of the rhubarb formula granules are further guaranteed. The rhubarb pieces were subjected to one warm soaking, two decoctions, and three extractions in total, which significantly improved the content and transfer rate of free anthraquinones and total anthraquinones in the rhubarb formula granules. The specific warm soaking and decoction times, the amount of water added, the warm soaking time, and the temperature also helped to improve the production efficiency and quality of the rhubarb formula granules. DETAILED DESCRIPTION

[0024] The following examples are provided for a better understanding of the present invention, but are not intended to limit the best mode of implementation, nor to limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior arts shall fall within the protection scope of the present invention.

[0025] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be obtained commercially.

[0026] According to the Technical Requirements for Quality Control and Standardization of Chinese Medicine Formula Granules issued by the State Food and Drug Administration: The production process research of Chinese medicine formula granules should be compared with the standard decoction, with the paste yield, fingerprint or characteristic spectrum, and consistency of the main component content as the inspection indicators, and the transfer of quantity and material balance in the preparation process of raw materials, intermediates and finished products should be comprehensively studied to determine various process parameters; the ultimate goal of process research is to ensure the quality consistency of finished Chinese medicine formula granules and standard decoctions. The paste yield range of rhubarb (medicinal rhubarb) formula granules is 14% to 25%, and the finished amount is 25%, which is formulated on the basis of multiple batches of standard decoction research. Therefore, the preparation process of rhubarb in the present invention must be based on the paste yield range of 14% to 25% and the finished amount of 25%. At the same time, the Technical Requirements for Quality Control and Standardization of Chinese Medicine Formula Granules also stipulates that the intermediate (extract or dry paste powder) link in the preparation process of Chinese medicine formula granules is designed to ensure the quality consistency between batches of the final product, so as to overcome the problem of uneven quality of the finished product caused by fluctuations in raw material quality and differences in preparation process; the intermediate of the formula granules can be blended and other treatments to solve the quality fluctuation problem caused by differences in preparation process. The extract after blending and treatment is granulated and formed again, which is a key process step to ensure the consistency between batches of Chinese medicine formula granules and maintain stable quality. In the present invention, the difference in the paste yield and other indicators in the intermediate (extract) link is caused by the difference in preparation process. In order to evaluate the link of rhubarb extract to granulation and forming, the present invention separately blends the extracts prepared in different embodiments and comparative examples, and uniformly uses the amount of preparation, which is reflected in the operation of discarding the part of dry extract powder that exceeds 25% of the amount of preparation, so as to better evaluate the difference in the quality attributes of the finished product due to the same granulation process due to differences in pre-treatment or extraction.

[0027] In the various embodiments and comparative examples of the present invention, the rhubarb medicinal materials used are all medicinal rhubarb.

[0028] Example 1

[0029] This embodiment provides a method for preparing rhubarb formula granules, which specifically comprises the following steps:

[0030] (1) Take rhubarb medicinal material, add room temperature water with an amount three times the weight of the rhubarb medicinal material, soak for 8 hours, take out, and cut into thick slices (average thickness of 3 mm, the same below) using a medicinal slicer to prepare rhubarb decoction slices.

[0031] (2) taking the rhubarb slices prepared in (1), adding water 8 times the weight of the rhubarb slices, and soaking at 80° C. for 15 minutes, filtering to obtain a first filtrate and a first filter residue;

[0032] (3) taking the first filter residue, adding water 20 times the weight of the rhubarb slices and boiling at 100° C. for 15 minutes, filtering to obtain a second filtrate and a second filter residue;

[0033] (4) taking the second filter residue, adding water 10 times the weight of the rhubarb slices and boiling at 100° C. for 15 minutes, filtering to obtain a third filtrate and a third filter residue;

[0034] (5) combining the first filtrate, the second filtrate, and the third filtrate, and concentrating under reduced pressure at -0.065 MPa and 75° C. to obtain a fluid paste with a relative density of 1.04 g / mL;

[0035] (6) The fluid paste obtained in (5) is spray dried at an air inlet temperature of 170°C and an air outlet temperature of 95°C to obtain a spray dried powder, which is then pulverized through a 100-mesh sieve to obtain a dry extract powder. The dry extract powder is added with auxiliary material maltodextrin, mixed evenly, and then dry granulated to obtain rhubarb formula granules.

[0036] Example 1 was repeated twice as a parallel experiment. The decoction liquid transfer time in each step was recorded. The specific liquid transfer operation was as follows: after each decoction extraction, the decoction was passed through a double filter, filtered through an 80-mesh filter, and the filtrate was transferred to a liquid storage tank. In the first experiment, the decoction liquid transfer time of step (2) was 20 minutes, the decoction liquid transfer time of step (3) was 30 minutes, and the decoction liquid transfer time of step (4) was 20 minutes, and 1.5 g of maltodextrin as an auxiliary material was added to the dry extract powder; in the second experiment, the decoction liquid transfer time of step (2) was 18 minutes, the decoction liquid transfer time of step (3) was 27 minutes, and the decoction liquid transfer time of step (4) was 18 minutes, and 1.3 g of maltodextrin as an auxiliary material was added to the dry extract powder.

[0037] Example 2

[0038] This embodiment provides a method for preparing rhubarb formula granules, which specifically comprises the following steps:

[0039] (1) Take rhubarb medicinal material, add room temperature water with an amount three times the weight of the rhubarb medicinal material, soak it for 8 hours, take it out, cut it into thick slices in a medicine cutting machine, and prepare rhubarb decoction slices.

[0040] (2) Take the rhubarb slices prepared in (1), add water 8 times the weight of the rhubarb slices, soak at 90°C for 15 minutes, filter, and obtain a first filtrate and a first filter residue. The decoction liquid conversion time is 18 minutes.

[0041] (3) Take the first filter residue, add 20 times the weight of the rhubarb slices of water and boil at 100°C for 15 minutes, filter, and obtain the second filtrate and the second filter residue. The decoction liquid conversion time is 27 minutes.

[0042] (4) Take the second filter residue, add 10 times the weight of the rhubarb slices of water and boil at 100°C for 15 minutes, filter, and obtain the third filtrate and the third filter residue. The decoction liquid conversion time is 18 minutes.

[0043] (5) The first filtrate, the second filtrate, and the third filtrate were combined and concentrated under reduced pressure at -0.066 MPa and 75° C. to obtain a fluid paste with a relative density of 1.04 g / mL.

[0044] (6) The fluid paste obtained in (5) is spray dried at an air inlet temperature of 170°C and an air outlet temperature of 95°C to obtain a spray dried powder, which is then pulverized through a 100-mesh sieve to obtain a dry extract powder. The dry extract powder is added with 1.3 g of auxiliary material maltodextrin, mixed evenly, and then dry granulated to obtain rhubarb formula granules.

[0045] Example 3

[0046] This embodiment provides a method for preparing rhubarb formula granules, which specifically comprises the following steps:

[0047] (1) Take rhubarb medicinal material, add 1 times the weight of rhubarb medicinal material in room temperature water, soak for 12 hours, take out, cut into thick slices in a medicine cutter, and prepare rhubarb decoction slices.

[0048] (2) Take the rhubarb slices prepared in (1), add 10 times the weight of the rhubarb slices of water, soak at 95°C for 5 minutes, filter, and obtain a first filtrate and a first filter residue. The decoction liquid conversion time is 25 minutes.

[0049] (3) Take the first filter residue, add 24 times the weight of the rhubarb slices of water and boil at 100°C for 5 minutes, filter, and obtain the second filtrate and the second filter residue. The decoction liquid conversion time is 35 minutes.

[0050] (4) Take the second filter residue, add 14 times the weight of the rhubarb slices of water and boil at 100°C for 5 minutes, filter, and obtain the third filtrate and the third filter residue. The decoction liquid conversion time is 25 minutes.

[0051] (5) The first filtrate, the second filtrate, and the third filtrate were combined and concentrated under reduced pressure at -0.067 MPa and 50° C. to obtain a fluid paste with a relative density of 1.01 g / mL.

[0052] (6) The fluid paste obtained in (5) is spray dried at an air inlet temperature of 172° C. and an air outlet temperature of 98° C. to obtain a spray dried powder, which is pulverized through a 100-mesh sieve to obtain a dry extract powder, which is dry granulated to obtain rhubarb formula granules.

[0053] Example 4

[0054] This embodiment provides a method for preparing rhubarb formula granules, which specifically comprises the following steps:

[0055] (1) Take rhubarb medicinal material, add 8 times the weight of rhubarb medicinal material water at room temperature and soak for 4 hours, then take it out and cut it into thick slices in a medicine cutting machine to prepare rhubarb decoction slices.

[0056] (2) Take the rhubarb slices prepared in (1), add water 6 times the weight of the rhubarb slices, soak at 80°C for 30 minutes, filter, and obtain a first filtrate and a first filter residue. The decoction liquid conversion time is 22 minutes.

[0057] (3) Take the first filter residue, add 16 times the weight of the rhubarb slices of water and boil at 98°C for 30 minutes, filter, and obtain the second filtrate and the second filter residue. The decoction liquid conversion time is 32 minutes.

[0058] (4) Take the second filter residue, add water 6 times the weight of the rhubarb slices, boil at 98°C for 30 minutes, filter, and obtain the third filtrate and the third filter residue. The decoction liquid conversion time is 16 minutes.

[0059] (5) The first filtrate, the second filtrate, and the third filtrate were combined and concentrated under reduced pressure at -0.068 MPa and 80° C. to obtain a fluid paste with a relative density of 1.12 g / mL.

[0060] (6) The fluid paste obtained in (5) is spray dried at an air inlet temperature of 170°C and an air outlet temperature of 96°C to obtain a spray dried powder, which is then pulverized through a 100-mesh sieve to obtain a dry extract powder. The dry extract powder is added with 0.7 g of auxiliary material dextrin, mixed evenly, and dry granulated to obtain rhubarb formula granules.

[0061] Example 5

[0062] This embodiment provides a method for preparing rhubarb formula granules, which specifically comprises the following steps:

[0063] (1) Take rhubarb medicinal material, add 8 times the weight of rhubarb medicinal material in room temperature water, soak for 8 hours, take out, cut into thick slices in a medicine cutter, and prepare rhubarb decoction slices.

[0064] (2) Take the rhubarb slices prepared in (1), add water 8 times the weight of the rhubarb slices, soak at 80°C for 15 minutes, filter, and obtain a first filtrate and a first filter residue. The decoction liquid conversion time is 25 minutes.

[0065] (3) Take the first filter residue, add 20 times the weight of the rhubarb slices of water and boil at 100°C for 15 minutes, filter, and obtain the second filtrate and the second filter residue. The decoction liquid conversion time is 30 minutes.

[0066] (4) Take the second filter residue, add 10 times the weight of rhubarb slices of water and boil at 100°C for 15 minutes, filter, and obtain the third filtrate and the third filter residue. The decoction liquid conversion time is 23 minutes.

[0067] (5) The first filtrate, the second filtrate, and the third filtrate were combined and concentrated under reduced pressure at -0.070 MPa and 75° C. to obtain a fluid paste with a relative density of 1.03 g / mL.

[0068] (6) The fluid paste obtained in (5) is spray dried at an air inlet temperature of 175°C and an air outlet temperature of 98°C to obtain a spray dried powder, which is then pulverized through a 100-mesh sieve to obtain a dry extract powder. The dry extract powder is added with 2.6 g of lactose as an auxiliary material, mixed evenly, and then dry granulated to obtain rhubarb formula granules.

[0069] Comparative Example 1

[0070] The present comparative example provides a method for preparing rhubarb formula granules, which is different from Example 1 only in that the step before cutting into thick slices in step (1) of the present comparative example is as follows: taking rhubarb medicinal materials, steaming them in a vacuum medicine moistening machine until softened, using steam heating without adding water, specifically steaming at 80° C. for 60 minutes; using 25 g of dry extract powder, and no auxiliary materials.

[0071] The decoction liquid transfer time in each step is: the decoction liquid transfer time in step (2) is 60 minutes, the decoction liquid transfer time in step (3) is 62 minutes, and the decoction liquid transfer time in step (4) is 50 minutes.

[0072] Comparative Example 2

[0073] This comparative example provides a method for preparing rhubarb formula granules, which specifically comprises the following steps:

[0074] (1) Take rhubarb medicinal materials, crush them and pass them through a 24-mesh sieve to prepare rhubarb decoction slices.

[0075] (2) Take the rhubarb slices prepared in (1), add 20 times the weight of the rhubarb slices of water, extract at 100°C for 30 minutes, filter, and obtain a filtrate. The decoction conversion time is 20 minutes.

[0076] (3) The filtrate obtained in (2) was concentrated under reduced pressure at -0.070 MPa and 75°C to obtain a fluid paste with a relative density of 1.06 g / mL.

[0077] (4) The fluid paste obtained in (3) was spray dried at an air inlet temperature of 180°C and an air outlet temperature of 99°C to obtain a spray dried powder, which was pulverized through a 100-mesh sieve to obtain a dry extract powder. 25 g of the dry extract powder was dry granulated to obtain rhubarb formula granules.

[0078] Comparative Example 3

[0079] This comparative example provides a method for preparing rhubarb formula granules, which is different from Example 1 only in that step (4) is not performed in this comparative example, and in step (5), the first filtrate and the second filtrate are combined for subsequent steps; and 4.7 g of maltodextrin is used as an auxiliary material.

[0080] The decoction liquid conversion time in each step is: the decoction liquid conversion time in step (2) is 18 minutes, and the decoction liquid conversion time in step (3) is 27 minutes.

[0081] Comparative Example 4

[0082] This comparative example provides a method for preparing rhubarb formula granules, which is different from Example 1 only in that the mass of water added in steps (2) and (4) is different. In step (2) of this comparative example, water 12 times the mass of the rhubarb slices is added, and in step (4), water 16 times the mass of the rhubarb slices is added; 25 g of dry extract powder is used, and no auxiliary materials are used.

[0083] The decoction liquid transfer time in each step is: the decoction liquid transfer time in step (2) is 25 minutes, the decoction liquid transfer time in step (3) is 30 minutes, and the decoction liquid transfer time in step (4) is 25 minutes.

[0084] Comparative Example 5

[0085] This comparative example provides a method for preparing rhubarb formula granules, which is different from Example 1 only in that the method for preparing rhubarb slices in step (1) is different. In this comparative example, step (1) is: taking rhubarb medicinal materials, crushing them and passing them through a 24-mesh sieve to prepare rhubarb slices; using 25g of dry extract powder and no auxiliary materials.

[0086] The decoction liquid conversion time in each step is: the decoction liquid conversion time in step (2) is 85 minutes, the decoction liquid conversion time in step (3) is 96 minutes, and the decoction liquid conversion time in step (4) is 89 minutes.

[0087] Comparative Example 6

[0088] This comparative example provides a method for preparing rhubarb formula granules, which is different from Example 1 only in that the processing temperature and method in step (2) are different. In step (2) of this comparative example, the decocting temperature is 100° C.; 25 g of dry extract powder is used, and no auxiliary materials are used.

[0089] The decoction liquid conversion time in each step is: the decoction liquid conversion time in step (2) is 45 minutes, the decoction liquid conversion time in step (3) is 35 minutes, and the decoction liquid conversion time in step (4) is 25 minutes.

[0090] Comparative Example 7

[0091] This comparative example provides a method for preparing rhubarb formula granules, which is different from Example 1 only in that the warm soaking or decoction time of step (2), step (3) and step (4) is different; the warm soaking time of step (2) of this comparative example is 60 minutes, and the decoction time of step (3) is 30 minutes; the decoction time of step (4) is 30 minutes; 25g of dry extract powder is used, and no auxiliary materials are used.

[0092] The decoction liquid conversion time in each step is: the decoction liquid conversion time in step (2) is 36 minutes, the decoction liquid conversion time in step (3) is 39 minutes, and the decoction liquid conversion time in step (4) is 32 minutes.

[0093] Test Example 1

[0094] Record the decoction conversion time used in the filtration step in each embodiment and comparative example, and count its process parameters. Determine the free anthraquinone content of rhubarb medicinal materials and the total anthraquinone content of rhubarb medicinal materials in each embodiment and comparative example (with reference to the 2020 edition of the Chinese Pharmacopoeia), the free anthraquinone content and the total anthraquinone content in the obtained rhubarb formula granules (with reference to the national standard YBZ-PFKL-2021032), weigh the initial rhubarb medicinal material feeding amount, the weight of the obtained extract powder after drying, and the weight of the obtained rhubarb formula granules. Measure and calculate the paste rate, calculate the particle yield, the particle free anthraquinone transfer rate, and the particle total anthraquinone transfer rate, and judge the quality of the obtained rhubarb formula granules. All data are shown in Tables 1 and 2.

[0095] The calculation formulas used for each data are as follows:

[0096] Extraction rate = weight of dry extract powder / initial amount of rhubarb medicinal material × 100%.

[0097] Granule yield = weight of rhubarb formula granules / initial rhubarb medicinal material input amount × 100%.

[0098] Transfer rate of free anthraquinone in particles = free anthraquinone content in particles (mg / g) × particle yield / free anthraquinone content in medicinal materials (%) / 1000 × 100%.

[0099] Total anthraquinone transfer rate of particles = total anthraquinone content of particles (mg / g) × particle yield / total anthraquinone content of medicinal materials (%) / 1000 × 100%.

[0100] The quality judgment standard (reference national standard YBZ-PFKL-2021032) is: the paste rate range is 14% to 25%, the free anthraquinone content range is 2.5 to 7.0 mg / g, and the total anthraquinone content range is 10 to 25 mg / g; if the paste rate or content is not within the range, it is unqualified, and if the paste rate and content are both within the range, it is qualified. In rhubarb formula granules, the main ingredient is free anthraquinone, such as laxative and antipyretic effects are mainly achieved by free anthraquinone, so when preparing rhubarb formula granules, more attention is paid to the free anthraquinone content and free anthraquinone transfer rate.

[0101] Table 1

[0102]

[0103] Table 2

[0104]

[0105]

[0106] As can be seen from Tables 1 and 2, the rhubarb pre-treatment method, decoction times, temperature, time, and water multiple all have an impact on the quality of rhubarb formula granules. From the two parallel experiments in Example 1, it can be found that there are certain differences in their liquid transfer time and quality indicators, but the difference is not large. The preparation method of rhubarb granules provided in this application is relatively stable. From the data of Example 1 and Comparative Example 1, it can be seen that the pre-treatment method in Comparative Example 1 is to cut thick slices after steaming, the liquid transfer time of the production and extraction process is long, the efficiency is low, and the index component content is affected, the free anthraquinone content of the granules is low, and the rhubarb formula granules are unqualified. From the data of Example 1 and Comparative Example 2, it can be seen that the pre-treatment method of Comparative Example 2 is crushing, only one decoction is performed, the efficiency is improved, but the decoction paste rate is too high, the free anthraquinone content of the granules is low, and the rhubarb formula granules are unqualified. Compared with Example 1, Comparative Example 3 only performs one less extraction, resulting in a lower paste rate, a low free anthraquinone content of the granules, a low free anthraquinone transfer rate of the granules, and the raw rhubarb medicinal materials are not fully extracted and utilized. Compared with Example 1, the difference between Comparative Example 4 and Example 1 is that the amount of water in the first and second extractions is increased, resulting in an increase in the water addition time and the liquid transfer time, which leads to a decrease in efficiency, and the paste rate is too high, and the rhubarb formula granules are unqualified. Compared with Example 1, the only difference between Comparative Example 5 and Example 1 is that the pretreatment method is crushing, which leads to a long liquid transfer time of each extraction, up to 90 minutes, a decrease in efficiency, and a low content of free anthraquinone in the particles, and the rhubarb formula granules are unqualified. Compared with Example 1, the only difference between Comparative Example 6 and Example 1 is that the first extraction is decocted at 100°C, which leads to an increase in the liquid transfer time, a decrease in efficiency, a high paste rate, and the rhubarb formula granules are unqualified, and the free anthraquinone transfer rate is low. Compared with Example 1, the difference between Comparative Example 7 and Example 1 is that in step (2), water 8 times the mass of the rhubarb slices is added and soaked at 80°C for 60 minutes; in step (3), the decocting time is 30 minutes; in step (4), the decocting time is 30 minutes. Since the warm soaking time of the first extraction is too long, even if the decoction time of the next two extractions is within the time specified in this application, it is inevitable that the liquid transfer time of each extraction is long, the efficiency is reduced, the paste yield is too high, the rhubarb formula granules are unqualified, the free anthraquinones are affected, the transfer rate is low, and the loss is large.

[0107] The rhubarb formula granules prepared by the method specified in the present application in the embodiments have high free anthraquinone content and high free anthraquinone transfer rate, and all the rhubarb formula granules are qualified; and the overall preparation process has a short liquid transfer time and smooth production.

[0108] Obviously, the above embodiments are merely examples for clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived therefrom are still within the protection scope of the invention.

Claims

1. A method for preparing rhubarb formula granules, characterized in that: The steps include: S1: Soaking rhubarb in water at room temperature, cutting into thick slices, and preparing rhubarb slices; S2: taking rhubarb slices, adding water 6 to 10 times the weight of the rhubarb slices, soaking at 65 to 95° C. for 5 to 30 minutes, filtering to obtain a first filtrate and a first filter residue; S3: boiling the first filter residue with water 16 to 24 times the mass of the rhubarb slices, filtering, and obtaining a second filtrate and a second filter residue; S4: boiling the second filter residue with water 6 to 14 times the mass of the rhubarb slices, filtering, and obtaining a third filtrate and a third filter residue; S5: combining the first filtrate, the second filtrate, and the third filtrate, and concentrating under reduced pressure to obtain a fluid paste; S6: drying and crushing the fluid paste, adding or not adding auxiliary materials thereto, granulating to obtain rhubarb formula granules.

2. The method for preparing the rhubarb formula granules according to claim 1, characterized in that: In S1, the rhubarb medicinal material is soaked in water at room temperature with a weight of 1 to 8 times that of the rhubarb medicinal material for 4 to 12 hours.

3. The method for preparing rhubarb formula granules according to claim 1 or 2, characterized in that: In S3, the boiling time is 5 to 30 minutes and the temperature is 98 to 100° C.; And / or, in S4, the decocting time is 5 to 30 minutes and the temperature is 98 to 100°C.

4. The method for preparing the rhubarb formula granules according to any one of claims 1 to 3, characterized in that: In said S5, the temperature of reduced pressure concentration is 50-80°C; And / or, in S6, the pulverizing is to pulverize the dried fluid paste to a particle size of ≤100 mesh.

5. The method for preparing the rhubarb formula granules according to any one of claims 1 to 4, characterized in that: In the above S5, the relative density of the obtained fluid paste is 1.01-1.12 g / mL.

6. The method for preparing the rhubarb formula granules according to any one of claims 1 to 5, characterized in that: The steps include: S1: Soak the rhubarb medicinal material in room temperature water with a weight of 1 to 3 times the weight of the rhubarb medicinal material for 4 to 8 hours, cut into thick slices, and prepare rhubarb decoction slices; S2: taking rhubarb slices, adding water 8 to 10 times the weight of the rhubarb slices, soaking at 80 to 95° C. for 5 to 15 minutes, filtering to obtain a first filtrate and a first filter residue; S3: boiling the first filter residue with water 20 to 24 times the mass of the rhubarb slices at 100° C. for 5 to 15 minutes, filtering to obtain a second filtrate and a second filter residue; S4: adding the second filter residue and water 10 to 14 times the mass of the rhubarb slices and boiling at 100° C. for 5 to 15 minutes, filtering to obtain a third filtrate and a third filter residue; S5: combining the first filtrate, the second filtrate, and the third filtrate, and concentrating under reduced pressure to obtain a fluid paste; S6: drying and crushing the fluid paste, adding or not adding auxiliary materials thereto, granulating to obtain rhubarb formula granules.

7. The method for preparing rhubarb formula granules according to any one of claims 1 to 6, characterized in that: The auxiliary material comprises at least one of dextrin, maltodextrin, beta-cyclodextrin, lactose, silicon dioxide and magnesium stearate.

8. The method for preparing rhubarb formula granules according to claim 7, characterized in that: The amount of the auxiliary material added is 0% to 11% of the mass of the rhubarb formula granules.

9. The method for preparing rhubarb formula granules according to any one of claims 1 to 8, characterized in that: In S6, the granulation method includes any one of dry granulation, wet granulation, and one-step granulation; And / or, in S6, the drying method includes spray drying.

10. A rhubarb formula granule prepared by the preparation method according to any one of claims 1 to 9.

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