Preparation method of traditional Chinese medicine decoction pieces of medicinal materials with high sugar content

Abstract

The invention relates to a preparation method of traditional Chinese medicine decoction pieces with high sugar content, which comprises the following steps: freezing the traditional Chinese medicine decoction pieces to prepare frozen traditional Chinese medicine decoction pieces; performing crushing treatment on the frozen traditional Chinese medicine decoction pieces to prepare crushed traditional Chinese medicine decoction pieces; and drying the crushed traditional Chinese medicine decoction pieces, sieving, and mixing with a flow aid to obtain the traditional Chinese medicine decoction pieces. The method is simple and easy to implement, high in production efficiency, low in cost, free of pollution and suitable for industrial production. Meanwhile, the decoction powder decoction pieces prepared by the method are good in fluidity, consistent in particle size, good in uniformity and good in stability, can effectively solve the problems that decoction pieces with high sugar content are easy to bond and agglomerate and are inconvenient to prepare clinically, and are beneficial to clinical preparation and use.

Description

Technical Field

[0001] The present application relates to the technical field of Chinese medicine preparations, and in particular to a method for preparing Chinese medicine decoction pieces of medicinal materials with high sugar content. Background Art

[0002] Chinese herbal medicine slices (hereinafter referred to as slices) are cut into various shapes, mainly slices, and are gradually replaced by traditional slices suitable for commercial packaging and sales and are still used today. The three major problems that restrict the development of clinical Chinese medicine with traditional slices are becoming increasingly prominent, namely: (1) The quality consistency of clinical prescription slices is poor. Traditional slices are affected by factors such as the origin, harvesting, transportation, storage, and processing of medicinal materials, resulting in large differences in the intra-batch and inter-batch quality of traditional Chinese medicine slices, which greatly affects the clinical treatment effect; (2) The pharmacy takes a long time to adjust, the efficiency is low, the error is large, and the storage and maintenance are difficult; (3) The decoction time of the slices is long, the decoction rate is low, and there is a lot of waste.

[0003] Guangdong Provincial Institute of Drug Control and Guangdong Provincial Association of Traditional Chinese Medicine have successively issued the "Guiding Principles and Technical Requirements for the Research of Quality Standards for Chinese Herbal Powder Pieces". So far, Guangdong Provincial Institute of Drug Control has publicly announced 15 quality standards for Chinese herbal powder pieces, and Guangdong Provincial Association of Traditional Chinese Medicine has issued 34 group quality standards for Chinese herbal powder pieces (published in 4 batches). The specific varieties and release time are as follows:

[0004]

[0005] Among them, on August 13, 2020, the Guangdong Provincial Drug Control Institute issued the "Guiding Principles and Technical Requirements for Quality Standards Research on Decocted and Powdered Chinese Medicines (Trial)", which clarified that cooked and powdered Chinese medicines are a form of medication in which Chinese medicinal materials are processed and made into coarse granules or coarse powders of 0.2mm to 10mm in size according to regulations, decocted in water, and the residue is removed to obtain the juice or taken together with the residue. For rhizome medicinal materials with hard and dense texture, they can be made into decocted and loose medicinal slices through crushers and other equipment. The preparation process is less difficult, and the prepared decocted and loose medicinal slices have good fluidity, which can achieve the purpose of facilitating preparation and saving medicinal materials, such as licorice, processed Polygonum multiflorum, Alisma orientale and Curcuma aromatica; for flower, leaf and whole herb medicinal materials with light, loose texture and large specific surface area, they can be made into decocted and loose medicinal slices through slicers, grinders and other equipment, and the effective ingredients are easier to decoct, such as mulberry leaves, chrysanthemums, Viola yedoensis and Leonurus japonicus; and some sticky and soft medicinal materials with high sugar content are difficult to prepare into coarse particles with uniform particle size because their surface is easy to adhere, their texture is soft and tough, and they are easy to stick together. For example, Rehmannia root, Cistanche deserticola, Polygonatum sibiricum, Lycium barbarum, jujube, etc. Summary of the invention

[0006] Based on this, it is necessary to provide a method for preparing Chinese herbal medicine slices with high sugar content, which is simple to operate and has high production efficiency. The prepared Chinese herbal medicine slices have good fluidity, good uniformity and good stability, and can effectively solve the problem that Chinese herbal medicine slices with high sugar content are easy to stick together and are inconvenient for clinical preparation.

[0007] The technical solution of this application is as follows:

[0008] One aspect of the present invention provides a method for preparing a Chinese medicine decoction piece of a medicinal material with a high sugar content, comprising the following steps:

[0009] Freezing the Chinese medicinal pieces of the medicinal material to prepare frozen Chinese medicinal pieces;

[0010] The frozen Chinese herbal medicine pieces are crushed to prepare crushed Chinese herbal medicine pieces;

[0011] The crushed Chinese herbal medicine pieces are dried, sieved and mixed with a flow aid to obtain the product.

[0012] In one embodiment, the freezing step satisfies at least one of the following conditions:

[0013] (1) The freezing temperature is -70℃~-20℃;

[0014] (2) The freezing time is 5h~24h.

[0015] In one embodiment, the drying step satisfies at least one of the following conditions:

[0016] (1) The drying temperature is 40℃~80℃;

[0017] (2) The drying time is 3h~10h.

[0018] In one embodiment, the mixing speed is 10 rpm to 20 rpm; and / or

[0019] The mixing time is 10 minutes to 30 minutes.

[0020] In one embodiment, the mass ratio of the glidant to the Chinese herbal medicine slices is 1% to 10%.

[0021] In one embodiment, the glidant comprises a co-processing glidant or a single glidant.

[0022] In one embodiment, the single glidant comprises silicon dioxide, colloidal silicon dioxide or gel silicon dioxide.

[0023] In one embodiment, the co-processed glidant includes a mannitol-crosslinked sodium carboxymethyl cellulose co-processed product, a microcrystalline cellulose-mannitol co-processed product, a calcium phosphate-waxy starch-microcrystalline cellulose co-processed product, or a microcrystalline cellulose-silica gel-carboxymethyl cellulose-sodium stearyl fumarate co-processed product.

[0024] In one embodiment, the medicinal materials include one or more of Rehmannia root, Cistanche deserticola, Polygonatum sibiricum, Lycium barbarum and jujube.

[0025] Another aspect of the present invention provides a Chinese herbal medicine decoction piece, which is prepared by the preparation method of the Chinese herbal medicine decoction piece of high-sugar-content medicinal materials as described above.

[0026] Compared with the prior art, this application has the following beneficial effects:

[0027] According to the characteristics of high-sugar-content sticky and soft medicinal materials, the present application provides a method for preparing Chinese medicinal decoction pieces of medicinal materials after reasonably setting the steps. The method is simple and easy to operate, has high production efficiency, low cost, no pollution, and is suitable for industrial production. At the same time, the decoction pieces prepared according to the method have good fluidity, consistent particle size, good uniformity, and good stability, which can effectively solve the problem that Chinese medicinal decoction pieces with high sugar content are easy to stick together and inconvenient for clinical preparation, and are conducive to clinical adjustment and use. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the specific implementation methods of the present application or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0029] Figure 1 This is a flow chart for preparing Rehmannia glutinosa powder slices according to an embodiment of the present application.

[0030] Figure 2 It is a comparison chart of Rehmannia glutinosa original slices and Rehmannia glutinosa boiled and powdered slices, wherein the left side is Rehmannia glutinosa original slices, and the right side is Rehmannia glutinosa boiled and powdered slices prepared in this application.

[0031] Figure 3 It is a characteristic spectrum diagram of the prepared Rehmannia root powder slices prepared in Examples 1 to 9. DETAILED DESCRIPTION

[0032] The present application is further described in detail below in conjunction with specific embodiments. The present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present application more thoroughly understood.

[0033] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0034] Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings:

[0035] As used herein, "one or more" refers to any one, any two, or any two or more of the listed items.

[0036] Herein, the optional scope of "and / or", "or / and", and "and / or" includes any one of two or more relevant listed items, and also includes any and all combinations of the relevant listed items, wherein said any and all combinations include any two relevant listed items, any more relevant listed items, or a combination of all relevant listed items. (It should be noted that when at least three items are connected by at least two conjunctions selected from "and / or", "or / and", and "and / or", it should be understood that in the present application, the technical solution undoubtedly includes technical solutions that are all connected by "logical AND", and also undoubtedly includes technical solutions that are all connected by "logical OR". For example, "A and / or B" includes three parallel solutions of A, B and A+B. For another example, the technical solution of "A, and / or, B, and / or, C, and / or, D" includes any one of A, B, C, and D (that is, technical solutions that are all connected by "logical OR"), and also includes any and all combinations of A, B, C, and D, that is, a combination of any two or any three of A, B, C, and D, and also includes a combination of four items of A, B, C, and D (that is, a technical solution that is all connected by "logical AND").)

[0037] Herein, "further", "further", "particularly" and the like are used for descriptive purposes to indicate differences in content, but should not be construed as limiting the scope of protection of this application.

[0038] In this application, when it comes to numerical ranges, unless otherwise specified, the above numerical ranges are deemed to be continuous and include the minimum and maximum values ​​of the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges included therein.

[0039] The percentage contents involved in this application, unless otherwise specified, refer to mass percentage for solid-liquid mixture and solid-solid mixture, and refer to volume percentage for liquid-liquid mixture.

[0040] The percentage concentrations mentioned in this application, unless otherwise specified, refer to the final concentration, which refers to the percentage of the added component in the system after the addition of the component.

[0041] The temperature parameters in this application, unless otherwise specified, allow both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows the temperature to fluctuate within the accuracy range controlled by the instrument. Fluctuations within the range of ±5°C, ±2°C, ±1°C, ±0.5°C, ±0.4°C, ±0.3°C, ±0.2°C, and ±0.1°C are allowed. Normal temperature or room temperature in this application refers to no temperature control operation, generally 4°C~35°C, preferably 20±5°C.

[0042] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0043] The preparation of boiled and loose medicinal slices is the process of crushing the Chinese medicines for decoction into a certain size and shape, which has the advantages of short decoction time and less energy loss, and can save medicinal resources very well. The materials after crushing and sieving are generally particles or powders of approximately the same size, which is not only conducive to uniform mixing, reducing the quality difference within the batch and the weight difference of the packaging, but also convenient for adjustment and decoction, which helps to improve the intrinsic quality of the medicine. Based on this, the technical personnel of this application, after a lot of research, provide a method for preparing boiled and loose medicinal slices that can effectively solve the problem of sticky and soft medicinal materials with high sugar content: the hardness of sticky and soft Chinese medicinal materials with high sugar content is increased by low-temperature freezing and then crushed to prepare boiled and loose medicinal slices, and the surface viscosity of the boiled and loose medicinal slices is reduced by drying and adding an appropriate amount and type of flow aid, thereby improving its fluidity and uniformity, improving the stability of product quality, and also achieving the effect of saving Chinese medicinal materials.

[0044] One aspect of the present invention provides a method for preparing a Chinese medicine decoction piece of a medicinal material with a high sugar content, comprising the following steps:

[0045] Freezing the Chinese medicinal pieces of the medicinal material to prepare frozen Chinese medicinal pieces;

[0046] The frozen Chinese herbal medicine pieces are crushed to prepare crushed Chinese herbal medicine pieces;

[0047] The crushed Chinese herbal medicine pieces are dried, sieved and mixed with a flow aid to obtain the product.

[0048] In some examples, the freezing treatment conditions include: the freezing temperature is -70°C to -20°C. It can be understood that the freezing temperature includes but is not limited to -70°C, -60°C, -50°C, -40°C, -30°C, and -20°C.

[0049] In some examples, the freezing treatment conditions include: the freezing time is 5 hours to 24 hours. It can be understood that the freezing time includes but is not limited to 5 hours, 10 hours, 13 hours, 15 hours, 18 hours, 20 hours, 22 hours, and 24 hours.

[0050] Particle size is an important parameter for quality control of boiled and dispersed medicines. The emphasis of boiled and dispersed medicine slices is "fine but not powdery". There are many ways to crush Chinese medicine, such as pounding, pulverizing and chopping. Modern crushing machines mainly include crushers, crushers, slicers, dicer, etc., depending on the shape of the crushed objects. The cutting methods include fresh cutting, dry cutting and moist cutting. The working principles of various crushing equipment are different, and their applicability is different when preparing boiled and dispersed medicine slices. Different crushing methods should be selected according to the crushing purpose and the texture of Chinese medicine materials, and further appropriate crushing equipment should be selected. However, a certain amount of fine powder is often produced during the crushing process. The uniformity of particle size and the amount of fine powder produced during the crushing process are mainly affected by four factors: ① It is related to the variety and material of Chinese medicine. The more starch, the higher the powder formation rate; ② It is related to the fineness of crushing. The finer the particle size, the more fine powder; ③ It is related to the working principle of the crusher. Different materials use different crushing machines; ④ It is related to the speed of the machine. The higher the speed, the higher the powder formation rate. Therefore, in order to obtain medicinal pieces that meet the particle size requirements, it is necessary to select appropriate crushing machinery and appropriate operating parameters according to the properties and texture of the medicinal materials. Compared with the conventional direct crushing method, the present application adopts a method of crushing after freezing, which has a smooth crushing process and can improve production efficiency, finished product yield and product quality.

[0051] In some of the examples, the mesh size used for sieving is 0.2 cm to 1.0 cm. It is understandable that the mesh size used for sieving includes but is not limited to 0.2 cm, 0.4 cm, 0.6 cm, 0.8 cm, and 1.0 cm.

[0052] In some examples, the drying conditions include: the drying temperature is 40° C. to 80° C. It can be understood that the drying temperature includes but is not limited to 40° C., 50° C., 60° C., 70° C., and 80° C.

[0053] In some examples, the drying conditions include: the drying time is 3 hours to 10 hours. It can be understood that the drying time includes but is not limited to 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, and 10 hours.

[0054] In some of these examples, the mixing speed is 10 rpm to 20 rpm. It is understandable that the mixing speed includes but is not limited to 10 rpm, 12 rpm, 14 rpm, 16 rpm, 18 rpm, and 20 rpm.

[0055] In some of these examples, the mixing time is 10 minutes to 30 minutes. It is understandable that the mixing time includes but is not limited to 10 minutes, 15 minutes, 20 minutes, 25 minutes, and 30 minutes.

[0056] Compared with the prior art, the method for preparing the decoction pieces of the present application has the following advantages:

[0057] (1) This application determines a reasonable range of process parameters for the preparation of decoction pieces by reasonably selecting freezing temperature, freezing time, crushing specifications, drying temperature, drying time, type and amount of flow aid, and mixing parameters.

[0058] (2) The present application adopts a method of crushing after freezing. Compared with the conventional direct crushing method, the crushing process is smooth, which can improve production efficiency, finished product yield and product quality.

[0059] (3) This application adopts the drying method to dry the crushed medicinal pieces and add an appropriate amount of flow aid, which can greatly improve the situation that sticky and soft medicinal materials are easy to stick together. The resulting boiled and dispersed medicinal pieces have the characteristics of good fluidity and uniform particle size, which is conducive to clinical adjustment and use.

[0060] In some of the examples, the mass ratio of the flow aid to the Chinese herbal medicine slices is 1% to 10%. Further, the mass ratio of the flow aid to the Chinese herbal medicine slices is 2% to 6%. It is understandable that the mass ratio of the flow aid to the Chinese herbal medicine slices includes but is not limited to 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, and 6%.

[0061] In some of these examples, the glidant includes a co-processing glidant or a single glidant.

[0062] In some of these examples, the single glidant includes silicon dioxide, colloidal silicon dioxide, or gel silicon dioxide.

[0063] In some of the examples, the co-processed flow aids include mannitol-cross-linked sodium carboxymethyl cellulose co-processed products, microcrystalline cellulose-mannitol co-processed products, calcium phosphate-waxy starch-microcrystalline cellulose co-processed products, or microcrystalline cellulose-silica gel-carboxymethyl cellulose-sodium stearyl fumarate co-processed products. The 2020 edition of the Chinese Pharmacopoeia 9603 Guiding Principles mentions that co-processed excipients refer to mixed excipients made from two or more pharmaceutical excipients through specific physical processing techniques (such as spray drying, granulation, etc.) to achieve specific functions. Through research, the technical personnel of this application have found that the use of a drying method to dry the crushed slices and adding an appropriate amount of flow aid can greatly improve the situation in which sticky and soft medicinal materials are prone to sticking together. Among them, the co-processed flow aid is more effective than a single flow aid, which is specifically reflected in the smaller angle of repose and better fluidity of the obtained Chinese herbal medicine slices.

[0064] In some examples, the medicinal materials include one or more of Rehmannia glutinosa, Cistanche deserticola, Polygonatum sibiricum, Lycium barbarum and jujube. It can be understood that the Chinese medicinal materials and Chinese medicinal pieces described in this application, in addition to the listed varieties, are also applicable to other Chinese medicinal varieties that are soft and not suitable for direct preparation into coarse particles.

[0065] In one specific example, the method for preparing the Chinese medicine decoction pieces of the high-sugar-content medicinal material comprises the following steps:

[0066] Step 1: Obtain Rehmannia glutinosa slices;

[0067] Step 2: placing the prepared Radix Rehmanniae slices in step 1 in an ultra-low temperature refrigerator and freezing them until they are hard and crisp, thereby obtaining "frozen prepared Radix Rehmanniae slices";

[0068] Step 3: putting the frozen cooked Rehmannia root slices obtained in step 2 into a crusher, inserting a sieve with a certain aperture to crush them into uniform particle sizes, and obtaining "crushed cooked Rehmannia root slices";

[0069] Step 4: placing the crushed Rehmannia glutinosa slices in step 3 in an oven for drying, sifting out the powder, and obtaining "dried Rehmannia glutinosa slices";

[0070] Step 5: placing the dried Radix Rehmanniae Radix slices prepared in step 4 into a mixer, and then adding a flow aid to mix the mixture, with a mixing speed of 15 rpm and a mixing time of 20 minutes, to obtain "Radix Rehmanniae Radix Powder Slices (to be packaged)";

[0071] Step 6: Collect the cooked Rehmannia root slices (to be packaged) and composite film from step 5, set the transverse sealing temperature, longitudinal sealing temperature and packaging speed of the packaging machine, select a suitable measuring cup, adjust the filling volume and then package; paste the printed label to obtain the "Cooked Rehmannia root slices".

[0072] In some of these examples, the filling volume difference and sealing should be checked regularly during the subpackaging in step 6. Step 6 also includes: receiving a blank label, entering the printed text, and starting printing after confirming that the first printed sample is correct. During printing, attention should be paid to checking the print quality.

[0073] Another aspect of the present invention provides a Chinese medicine decoction piece, which is prepared by the preparation method of Chinese medicine decoction piece with high sugar content as described above. Specifically, the Chinese medicine decoction piece prepared in the present application has the following advantages compared with the original decoction piece:

[0074] (1) The obtained Chinese herbal medicine pieces have good fluidity and uniform particle size, which is conducive to clinical adjustment and use. The quality uniformity of samples within the batch is significantly improved, including the stability of clinical efficacy;

[0075] (2) The dissolution of active ingredients is significantly improved, which can reduce the amount of clinical decoction pieces used and thus save Chinese medicinal materials.

[0076] (3) The quality stability of the obtained Chinese herbal medicine pieces is significantly improved. Within a certain storage time range, the original pieces are prone to sticking and agglomeration in a short period of time; while the pieces prepared according to the method of the present application can maintain a good state for a long time, with good fluidity and good product stability.

[0077] The following is further described in conjunction with specific embodiments. The raw materials involved in the following specific embodiments, unless otherwise specified, can all be commercially available; the instruments used, unless otherwise specified, can all be commercially available; the processes involved, unless otherwise specified, are all routinely selected by those skilled in the art.

[0078] Rehmannia glutinosa slices can be purchased from Anhui Runfurong Pharmaceutical Co., Ltd., Hebei Huaxu Pharmaceutical Co., Ltd., Sinopharm Fengliaoxing (Foshan) Pharmaceutical Co., Ltd. and other Chinese medicine slice production enterprises;

[0079] Silicon dioxide can be purchased from pharmaceutical excipient manufacturers such as Huzhou Zhanwang Pharmaceutical Co., Ltd., Anhui Shanhe Pharmaceutical Excipients Co., Ltd., and Shandong Liaocheng Ahua Pharmaceutical Co., Ltd.;

[0080] Colloidal silica can be purchased from pharmaceutical excipient manufacturers such as Hubei Huifu Nanomaterials Co., Ltd., Cabot Corporation, and Evonik Specialty Chemicals (Shanghai) Co., Ltd.

[0081] Gel silica can be purchased from pharmaceutical excipient manufacturers such as Grace Trading (Shanghai) Co., Ltd. Examples 1 to 9 are based on Figure 1 The flowchart shown is used to prepare Rehmannia glutinosa powder slices, and the following is a specific example.

[0082] Example 1

[0083] The present embodiment provides a method for preparing Rehmannia glutinosa slices, wherein the raw materials include Rehmannia glutinosa slices and a mannitol-crosslinked sodium carboxymethyl cellulose co-processed product, and the method comprises the following steps:

[0084] Take the Rehmannia glutinosa slices and place them in a -50℃ refrigerator, freeze for 6.0h, take them out and quickly put them into a crusher equipped with a 0.8cm screen to crush them to get the "crushed Rehmannia glutinosa slices"; take the "crushed Rehmannia glutinosa slices", spread them out, place them in an 80℃ oven for 8.0h, sieve out the fine powder, place them in a mixer, add 4% mannitol-cross-linked sodium carboxymethyl cellulose to mix, mix at a speed of 15 rpm, mix for 20 minutes, package, and label them. Observe the obtained Rehmannia glutinosa slices and Rehmannia glutinosa slices, and the results are as follows: Figure 2 As shown by Figure 2 It can be seen that the obtained boiled and dispersed medicinal pieces have good fluidity and consistent particle size.

[0085] Example 2

[0086] The present embodiment provides a method for preparing Rehmannia glutinosa slices, wherein the raw materials for preparation include Rehmannia glutinosa slices and microcrystalline cellulose-mannitol co-processed product, and the method comprises the following steps:

[0087] Take the cooked Rehmannia slices, place them in a -50℃ refrigerator, freeze them for 12.0h, take them out and quickly put them into a crusher equipped with a 0.8cm sieve to crush them to obtain "crushed cooked Rehmannia slices"; take the "crushed cooked Rehmannia slices", spread them out, place them in an 80℃ oven for 6.0h, sieve out the fine powder, place them in a mixer, add 2% of the slice amount of microcrystalline cellulose-mannitol to mix, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "cooked Rehmannia slices".

[0088] Example 3

[0089] The present embodiment provides a method for preparing Rehmannia glutinosa slices, wherein the raw materials include Rehmannia glutinosa slices and a mannitol-crosslinked sodium carboxymethyl cellulose co-processed product, and the method comprises the following steps:

[0090] Take the cooked Rehmannia slices, place them in a -30℃ refrigerator, freeze them for 12.0h, take them out and quickly put them into a crusher equipped with a 0.8cm sieve to crush them to obtain "crushed cooked Rehmannia slices"; take the "crushed cooked Rehmannia slices", spread them out, place them in an 80℃ oven for 6.0h, sieve out the fine powder, place them in a mixer, add 6% mannitol-cross-linked sodium carboxymethyl cellulose to mix, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "cooked Rehmannia slices".

[0091] Example 4

[0092] The present embodiment provides a method for preparing Rehmannia glutinosa slices, wherein the raw materials for preparation include Rehmannia glutinosa slices and colloidal silicon dioxide, and the method comprises the following steps:

[0093] Take the cooked Rehmannia slices, place them in a -30℃ refrigerator, freeze them for 12.0h, take them out and quickly put them into a crusher equipped with a 0.8cm sieve to crush them to obtain "crushed cooked Rehmannia slices"; take the "crushed cooked Rehmannia slices", spread them out, place them in an 80℃ oven for 6.0h, sieve out the fine powder, place them in a mixer, add 6% of the slice amount of colloidal silicon dioxide to mix, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "cooked Rehmannia slices".

[0094] Example 5

[0095] The present embodiment provides a method for preparing Rehmannia glutinosa slices, wherein the raw materials include Rehmannia glutinosa slices and a mannitol-crosslinked sodium carboxymethyl cellulose co-processed product, and the method comprises the following steps:

[0096] Take the cooked Rehmannia slices, place them in a -30℃ refrigerator, freeze them for 18.0h, take them out and quickly put them into a crusher equipped with a 0.8cm sieve to crush them to obtain "crushed cooked Rehmannia slices"; take the "crushed cooked Rehmannia slices", spread them out, place them in an 80℃ oven for 8.0h, sieve out the fine powder, place them in a mixer, add 4% mannitol-cross-linked sodium carboxymethyl cellulose to mix, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "cooked Rehmannia slices".

[0097] Example 6

[0098] The present embodiment provides a method for preparing Rehmannia glutinosa slices, wherein the raw materials include Rehmannia glutinosa slices and a mannitol-crosslinked sodium carboxymethyl cellulose co-processed product, and the method comprises the following steps:

[0099] Take the cooked Rehmannia slices, place them in a -50℃ refrigerator, freeze them for 6.0 hours, take them out and quickly put them into a crusher equipped with a 0.8 cm sieve to crush them to obtain "crushed cooked Rehmannia slices"; take the "crushed cooked Rehmannia slices", spread them out, place them in a 50℃ oven for 5.0 hours, sieve out the fine powder, place them in a mixer, add 6% mannitol-cross-linked sodium carboxymethyl cellulose to mix, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "cooked Rehmannia slices".

[0100] Example 7

[0101] The present embodiment provides a method for preparing Rehmannia glutinosa slices, wherein the raw materials include Rehmannia glutinosa slices and a mannitol-crosslinked sodium carboxymethyl cellulose co-processed product, and the method comprises the following steps:

[0102] Take the cooked Rehmannia slices, place them in a -50℃ refrigerator, freeze them for 6.0 hours, take them out and quickly put them into a crusher equipped with a 0.8 cm sieve to crush them to obtain "crushed cooked Rehmannia slices"; take the "crushed cooked Rehmannia slices", spread them out, place them in a 60℃ oven for 5.0 hours, sieve out the fine powder, place them in a mixer, add 2% mannitol-cross-linked sodium carboxymethyl cellulose to mix, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "cooked Rehmannia slices".

[0103] Example 8

[0104] The present embodiment provides a method for preparing Rehmannia glutinosa slices, wherein the raw materials for preparation include Rehmannia glutinosa slices and silicon dioxide, and the method comprises the following steps:

[0105] Take the cooked Rehmannia slices, place them in a -50℃ refrigerator, freeze them for 6.0 hours, take them out and quickly put them into a crusher equipped with a 0.8 cm sieve to crush them to obtain "crushed cooked Rehmannia slices"; take the "crushed cooked Rehmannia slices", spread them out, place them in a 60℃ oven for 5.0 hours, sieve out the fine powder, place them in a mixer, add 2% of silicon dioxide in the amount of the slices to mix, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "cooked Rehmannia slices".

[0106] Example 9

[0107] The present embodiment provides a method for preparing Rehmannia glutinosa slices, wherein the raw materials for preparation include Rehmannia glutinosa slices and microcrystalline cellulose-mannitol co-processed product, and the method comprises the following steps:

[0108] Take the cooked Rehmannia slices, place them in a -50℃ refrigerator, freeze them for 6.0 hours, take them out and quickly put them into a crusher equipped with a 0.8 cm sieve to crush them to obtain "crushed cooked Rehmannia slices"; take the "crushed cooked Rehmannia slices", spread them out, place them in a 70℃ oven for 8.0 hours, sieve out the fine powder, place them in a mixer, add 2% of the slice amount of microcrystalline cellulose-mannitol to mix, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "cooked Rehmannia slices".

[0109] Comparative Example 1

[0110] This comparative example provides a method for preparing Rehmannia glutinosa slices, the preparation raw materials comprising: Rehmannia glutinosa slices, comprising the following steps:

[0111] Take Rehmannia root slices, put them into a crusher equipped with a 0.8 cm sieve, and crush them to obtain "crushed Rehmannia root slices"; take the "crushed Rehmannia root slices", put them into a mixer for mixing, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "Cooked Rehmannia root slices".

[0112] Comparative Example 2

[0113] This comparative example provides a method for preparing Rehmannia glutinosa slices, the preparation raw materials comprising: Rehmannia glutinosa slices, comprising the following steps:

[0114] Take the prepared Rehmannia root slices, place them in a -50°C refrigerator, freeze them for 10.0h, take them out and quickly put them into a crusher equipped with a 0.8cm sieve to crush them to obtain "crushed Rehmannia root slices"; take the "crushed Rehmannia root slices" and place them in a mixer for mixing at a mixing speed of 15 rpm and a mixing time of 20 minutes. Package them and label them to obtain "prepared Rehmannia root slices".

[0115] Comparative Example 3

[0116] This comparative example provides a method for preparing Rehmannia glutinosa slices, the preparation raw materials comprising: Rehmannia glutinosa slices, mannitol-crosslinked sodium carboxymethyl cellulose co-processed product, comprising the following steps:

[0117] Take the prepared Rehmannia root slices, place them in a -50°C refrigerator, freeze them for 10.0 hours, take them out and quickly put them into a crusher equipped with a 0.8 cm screen to crush them to obtain "crushed Rehmannia root slices"; take the "crushed Rehmannia root slices", place them in a mixer, add 4% mannitol-cross-linked sodium carboxymethyl cellulose to mix them, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "prepared Rehmannia root slices".

[0118] Comparative Example 4

[0119] This comparative example provides a method for preparing Rehmannia glutinosa slices, the preparation raw materials comprising: Rehmannia glutinosa slices, mannitol-crosslinked sodium carboxymethyl cellulose co-processed product, comprising the following steps:

[0120] Take the cooked Rehmannia slices, place them in a -50℃ refrigerator, freeze them for 8.0h, take them out and quickly put them into a crusher equipped with a 0.8cm sieve to crush them to obtain "crushed cooked Rehmannia slices"; take the "crushed cooked Rehmannia slices", spread them out, place them in a 60℃ oven for 5.0h, sieve out the fine powder, place them in a mixer, add 0.2% mannitol-cross-linked sodium carboxymethyl cellulose to mix, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "cooked Rehmannia slices".

[0121] Comparative Example 5

[0122] This comparative example provides a method for preparing Rehmannia glutinosa slices, the preparation raw materials comprising: Rehmannia glutinosa slices, mannitol-crosslinked sodium carboxymethyl cellulose co-processed product, comprising the following steps:

[0123] Take the prepared Rehmannia root slices, place them in a -30℃ refrigerator, freeze them for 2.0h, take them out and quickly put them into a crusher equipped with a 0.8cm sieve to crush them to obtain "crushed Rehmannia root slices"; take the "crushed Rehmannia root slices", place them in a mixer, add 4% mannitol-cross-linked sodium carboxymethyl cellulose to mix them, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "prepared Rehmannia root slices".

[0124] Comparative Example 6

[0125] This comparative example provides a method for preparing Rehmannia glutinosa slices, the preparation raw materials comprising: Rehmannia glutinosa slices, mannitol-crosslinked sodium carboxymethyl cellulose co-processed product, comprising the following steps:

[0126] Take the cooked Rehmannia slices, place them in a -50℃ refrigerator, freeze them for 6.0 hours, take them out and quickly put them into a crusher equipped with a 0.8 cm sieve to crush them to obtain "crushed cooked Rehmannia slices"; take the "crushed cooked Rehmannia slices", spread them out, place them in a 60℃ oven for 2.0 hours, sieve out the fine powder, place them in a mixer, add 4% mannitol-cross-linked sodium carboxymethyl cellulose to mix, the mixing speed is 15 rpm, the mixing time is 20 minutes, package them, and label them to obtain "cooked Rehmannia slices".

[0127] The performance of the Rehmannia glutinosa powder prepared in Examples 1 to 9 and Comparative Examples 1 to 6 was evaluated, and the evaluation index detection method was as follows:

[0128]

Processing yield

[0129] [Mist content of medicinal slices] Determined by the drying method according to the second method under Item 0832 of the General Rules of Part IV of the 2020 Edition of the Chinese Pharmacopoeia, it shall not exceed 15.0%.

[0130] Water content of the slices = ×100%

[0131] [Extract from medicinal pieces] Determined by the cold infusion method under the determination of water-soluble extract (General Rules 2201, Part IV of the 2020 edition of the Chinese Pharmacopoeia), it shall not be less than 65.0%.

[0132] Extract of decoction pieces % = ×100%

[0133] [Oil yield] Determine according to the method for determination of water-soluble extract (General Rule 2201 of the 2020 edition of the Chinese Pharmacopoeia). Accurately pipette 25 mL of the decoction and place it in an evaporating dish M that has been dried to constant weight. 1 After evaporation on a water bath, dry at 105°C for 3 hours, cool in a desiccator for 30 minutes, and quickly and accurately weigh the weight M 2The amount of decoction pieces is M, the volume of decoction is V, and the calculation formula of the paste yield is as follows.

[0134] Paste yield (%) =

[0135] [Alcohol solubility] Accurately pipette 50 ml of the decoction into a 250 ml stoppered conical flask, add 95% ethanol while stirring to make the solution 70% concentrated, and let it stand for more than 12 hours. Filter and separate the supernatant, take 50 ml of the filtrate, place it in an evaporating dish that has been dried to constant weight, evaporate it on a water bath, dry it at 105 ° C for 3 hours, cool it in a desiccator for 30 minutes, and quickly and accurately weigh it. The formula for calculating the alcohol solubility is as follows.

[0136] Alcohol solubility (%) =

[0137] [Content Determination] Determined by high performance liquid chromatography (General Rules 0512, Part IV, 2020 Edition of the Chinese Pharmacopoeia).

[0138] Chromatographic conditions and system suitability test: Octadecylsilane bonded silica gel was used as filler; methanol-0.1% phosphoric acid solution (5:95) was used as mobile phase, and the detection wavelength was 203 nm. The theoretical plate number calculated based on the rehmannia glutinosin D peak should be no less than 5000.

[0139] Preparation of reference solution: Take an appropriate amount of Rehmannia glutinosin D reference substance, weigh it accurately, and add 25% methanol to make a solution containing 70 μg per 1 mL.

[0140] Preparation of test solution of medicinal materials and decoction pieces: take about 1g of crude powder of medicinal materials and decoction pieces, weigh it accurately, put it in a stoppered conical flask, accurately add 25mL of 25% methanol, weigh it, ultrasonically treat it (power 400W, frequency 50kHz) for 1 hour, cool it, weigh it again, make up the lost weight with 25% methanol, shake it well, centrifuge it at high speed for 10 minutes, filter the supernatant, and take the filtrate to obtain it.

[0141] Preparation of decoction test solution: accurately pipette 7.5 mL of the extract into a 10 mL volumetric flask, add methanol to make up to the mark, ultrasonically treat (power 400 W, frequency 50 kHz) for 1 hour, take out, cool, shake well, filter, and obtain the filtrate.

[0142] Determination method: Accurately pipette 10 μL of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0143] [Characteristic spectrum] Determined according to high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition, Part IV, General Rules 0512).

[0144] Chromatographic conditions and system suitability test: octadecylsilane bonded silica gel was used as filler (column length was 100 mm, inner diameter was 2.1 mm, particle size was 1.8 µm); acetonitrile was used as mobile phase A, 0.1% acetic acid solution was used as mobile phase B, and gradient elution was performed according to the provisions in Table 1; the flow rate was 0.3 mL per minute; the column temperature was 35 °C; the detection wavelength was 330 nm, and the elution procedure was as shown in Table 1. The theoretical plate number calculated based on the verbascoside peak should be no less than 5000.

[0145] Table 1

[0146]

[0147] Preparation of reference solution: Take 1g of Radix Rehmanniae glutinosae reference medicinal material, place it in a stoppered conical flask, add 100mL of methanol, heat and reflux for 1.5 hours, cool, shake, filter, accurately measure 50mL of the filtrate, recover the solvent under reduced pressure until it is almost dry, dissolve the residue in a mixed solution of acetonitrile-0.1% acetic acid solution (16:84), transfer it to a 5mL volumetric flask, add a mixed solution of acetonitrile-0.1% acetic acid solution (16:84) to the scale, shake, filter, and take the filtrate as the reference medicinal material reference solution. Take an appropriate amount of verbascoside reference substance, accurately weigh it, add methanol to make a solution containing 10µg per 1mL, and use it as the reference substance solution.

[0148] Preparation of test solution: Take 1 g of the powder of this product and prepare the reference solution of the control medicinal material.

[0149] Determination method: Accurately pipette 1µL of reference solution and 4µL of test solution respectively, inject into liquid chromatograph, and determine.

[0150] [Determination of repose angle] Determination is carried out by fixed funnel method. Fix the funnel on the iron frame, and fix H at 3.0cm from the bottom surface. Slowly pour the sample into the funnel, and the sample flows out from the outlet. When the top of the cone formed by the sample is about to be tangent to the bottom of the funnel, adjust the H value so that the top of the cone formed by the sample is tangent to the bottom of the funnel, measure the diameter of the cone bottom circle, record the H value, and calculate the repose angle. It is generally believed that when the repose angle is less than 40°, the fluidity is acceptable.

[0151] [Quality Uniformity] According to the sampling method for medicinal materials and decoction pieces under (General Rules of Part IV of the 2020 Edition of the Chinese Pharmacopoeia 0211), 500 g of the raw material Rehmannia glutinosa slices were taken, evenly flattened, divided into 9 portions, each portion took about 20 g, numbered a-1, a-2, a-3, a-4, a-5, a-6, a-7, a-8, a-9; take the "Rehmannia glutinosa slices" prepared in Example 1, randomly select 9 packages, numbered b-1, b-2, b-3, b-4, b-5, b-6, b-7, b-8, b-9, and determine the contents of the extracts and rehmannoside D according to the methods under [Decoction piece extracts] and [Content determination], and calculate the RSD, and compare the intra-batch quality difference results.

[0152] [Comparison of dissolution of boiled and loose slices and original slices] Take appropriate amounts of boiled and loose slices of Rehmannia glutinosa and original slices of Rehmannia glutinosa, refer to the relevant requirements of the "Management Specifications for Chinese Medicine Decoction Rooms in Medical Institutions" and "Technical Requirements for Quality Control and Standardization of Chinese Medicine Formula Granules", and determine the decoction process as follows: add water and decoct twice, add 9 times the amount of water for the first time, soak for 30 minutes, heat and decoct for 60 minutes, filter the decoction through a 350-mesh sieve while hot, add 7 times the amount of water for the second time, heat and decoct for 45 minutes, filter the decoction through a 350-mesh sieve, and combine the two filtrates. Each specification of slice sample was decocted in parallel for 3 times, and the amount of slices used in each group was about 100g, and the decoction's paste yield, alcohol solubility, and rehmannia glycoside D content were determined.

[0153] [Comparison of stability of boiled and loose slices and original slices] Take appropriate amount of packaged boiled and loose slices of Rehmannia glutinosa and original slices of Rehmannia glutinosa, place in a warehouse with a temperature of 25±2℃ and a relative humidity of 60±10%, and take samples at 0 month, 3 months, 6 months, 9 months and 12 months to check the properties of the two slices.

[0154] The performance evaluation results are shown in Table 2~Table 7. Figure 3 Shown

[0155] Table 2 Results of the Example of Rehmannia glutinosa Powder

[0156]

[0157] Table 3 Comparative results of Rehmannia glutinosa powder slices

[0158]

[0159] Table 4 Results of intra-batch quality difference test of Radix Rehmanniae Radix Pieces

[0160]

[0161] Table 5 Results of intra-batch quality difference test of Rehmannia glutinosa decoction pieces

[0162]

[0163] Table 6 Comparative study results of dissolution of Rehmannia glutinosa raw slices and cooked slices

[0164]

[0165] Table 7 Comparative study results on the stability of Rehmannia glutinosa raw slices and cooked slices

[0166]

[0167] From the results of Example 1 to Example 9 in Table 2, it can be seen that the crushing effect of Rehmannia glutinosa in each embodiment is good when the freezing temperature is -70℃~-20℃ and the freezing time is 5h~24h. The "crushed Rehmannia glutinosa slices" are baked at a temperature of 40℃~80℃ and a baking time of 3.0h~10.0h. After adding an appropriate amount of flow aid (co-processing flow aid or single flow aid) for mixing, the surface viscosity of the slices is small, fine powder can be sieved off, and the fluidity is good. The co-processing flow aid is better than the single flow aid (the smaller the repose angle, the better the fluidity), and the obtained boiled and scattered slice samples are convenient for clinical preparation and use. And the processing yield is relatively stable, all above 95%. From the test data, the indicators such as moisture, extract, content, and characteristic spectrum of each boiled and scattered slice are not significantly different from those of the raw materials.

[0168] As shown in Table 3, in Comparative Example 1, the direct crushing method was used. Since the texture of the Rehmannia glutinosa slices was sticky and soft, they were squeezed into a mass when crushed, and the material could not be fed. The crushing failed to be effective, and the desired decoction pieces could not be obtained. Comparative Example 2 was crushed after freezing at -50°C for 10.0h, without baking or adding a flow aid. The obtained sample had high viscosity, was easy to agglomerate, and had poor fluidity. Comparative Example 3 was crushed after freezing at -50°C for 10.0h, without baking. Although a flow aid was added, the obtained sample had high viscosity, was easy to agglomerate, and had poor fluidity. The properties of the samples were poor; Comparative Example 4 was crushed after freezing at -50°C for 8.0h and then dried at 60°C for 5.0h, but the amount of flow aid added was small, the obtained sample was easy to stick together, and the fluidity was not significantly improved; Comparative Example 5 was crushed after freezing at -30°C for 2.0h, the pieces quickly returned to room temperature, the crushing effect was poor, most of them could not pass through the 0.8cm sieve or adhered to the sieve, and the processing yield was low; Comparative Example 6 was crushed at low temperature and dried at 60°C for 2.0h, the surface viscosity of the pieces was improved, but the fluidity was still poor. The processing yields of Comparative Examples 1 to 6 were all low.

[0169] It can be seen from the results of the intra-batch quality difference test of the original and boiled pieces of Rehmannia glutinosa (Table 4 and Table 5) that the intra-batch quality difference of the boiled pieces prepared in Example 1 is significantly smaller than the intra-batch quality difference of the original pieces. Therefore, preparing Rehmannia glutinosa into boiled pieces with a uniform particle size range can effectively reduce the intra-batch quality difference and improve the uniformity of the finished product.

[0170] As shown in Table 6, the boiled and dispersed slices of Rehmannia glutinosa and the original slices of Rehmannia glutinosa were decocted under the same conditions. The decoction yield, alcohol solubility, rehmannia glycoside D content and total amount were compared. The boiled and dispersed slices were better than the original slices, indicating that the boiled and dispersed slices can save the amount of the original slices, thereby achieving the purpose of saving medicinal materials.

[0171] It can be seen from Table 7 that the prepared Rehmannia glutinosa slices prepared according to the method of the present application still have good fluidity after being placed at a temperature of 25±2°C and a relative humidity of 60±10% for 12 months, indicating that the prepared Rehmannia glutinosa slices have good stability.

[0172] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0173] The above-described embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be construed as limiting the scope of the patent application. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent application shall be subject to the attached claims, and the description may be used to interpret the content of the claims.

Claims

1. A method for preparing a Chinese medicine decoction piece of a high-sugar-content medicinal material, characterized in that: The following steps are involved: Freezing the Chinese medicinal pieces of the medicinal material to prepare frozen Chinese medicinal pieces; The frozen Chinese herbal medicine pieces are crushed to prepare crushed Chinese herbal medicine pieces; The crushed Chinese herbal medicine pieces are dried, sieved and mixed with a flow aid.

2. The method for preparing the Chinese medicinal decoction pieces of high-sugar-content medicinal materials according to claim 1, characterized in that: The freezing step satisfies at least one of the following conditions: (1) The freezing temperature is -70℃~-20℃; (2) The freezing time is 5h~24h.

3. The method for preparing the Chinese medicinal decoction pieces of high-sugar-content medicinal materials according to claim 1, characterized in that: The drying step satisfies at least one of the following conditions: (1) The drying temperature is 40℃~80℃; (2) The drying time is 3h~10h.

4. The method for preparing the Chinese medicinal decoction pieces of high-sugar-content medicinal materials according to claim 1, characterized in that: The mixing speed is 10 rpm to 20 rpm; and / or The mixing time is 10 minutes to 30 minutes.

5. The method for preparing the Chinese medicinal decoction pieces of high-sugar-content medicinal materials according to claim 1, characterized in that: The mass ratio of the flow aid to the Chinese herbal medicine slices is 1% to 10%.

6. The method for preparing the Chinese medicinal decoction pieces of high-sugar-content medicinal materials according to any one of claims 1 to 5, characterized in that: The glidant includes a co-processing glidant or a single glidant.

7. The method for preparing the Chinese medicinal decoction pieces of high-sugar-content medicinal materials according to claim 6, characterized in that: The single glidant includes silicon dioxide, colloidal silicon dioxide or gel silicon dioxide.

8. The method for preparing the Chinese medicinal decoction pieces of high-sugar-content medicinal materials according to claim 6, characterized in that: The co-processing glidant includes a mannitol-crosslinked sodium carboxymethyl cellulose co-processing product, a microcrystalline cellulose-mannitol co-processing product, a calcium phosphate-waxy starch-microcrystalline cellulose co-processing product, or a microcrystalline cellulose-silica gel-carboxymethyl cellulose-sodium stearyl fumarate co-processing product.

9. The method for preparing the Chinese medicinal decoction pieces of high-sugar-content medicinal materials according to any one of claims 1 to 5, characterized in that: The medicinal materials include one or more of Rehmannia root, Cistanche deserticola, Polygonatum sibiricum, Lycium barbarum and jujube.

10. A Chinese medicine decoction piece, characterized in that: The medicine is prepared by the method for preparing the Chinese medicinal decoction pieces of high-sugar-content medicinal materials according to any one of claims 1 to 9.

Images