Ryokeijutsukanto extract and its manufacturing method

Abstract

The present invention provides a Rikkeijutsu Kanto extract and a method for preparing the same. The extract comprises Rikkeijutsu Kanto extract powder and additives including maltodextrin and fine silica gel, with a modified ratio of extract powder:maltodextrin:fine silica gel of 64-74:25-39:1. The preparation method improves the moisture-proof and direct-pressing properties of the Rikkeijutsu Kanto extract powder, effectively improving the subsequent formulation process of Rikkeijutsu Kanto.

Description

[Technical Field]

[0001] The present invention relates to the field of traditional Chinese medicine preparation, and more particularly to a method for preparing a ryo-keizhuang-gan-tang extract. [Background technology]

[0002] The prescription for Liqing-Cui-Zhu-Gan Tang originates from Zhang Zhongjing's Treatise on Febrile and Miscellaneous Diseases. Article 67 of the book states, "For patients with typhoid fever, vomiting, or diarrhea followed by fullness below the heart, rising qi and pounding in the chest, dizziness when standing, a deep and tight pulse, sweating that activates the meridians, and trembling body movements, Poria Cocos, Gui Zhi, White Atractylodes Caesar Decoction is the primary treatment." The Jingui Yaolue also states, "For patients with phlegm and fluid below the heart, fullness in the chest and sides, and dizziness, Liqing-Cui-Zhu-Gan Tang is the primary treatment." Liqing-Cui-Zhu-Gan Tang is a dehumidifying agent with the effects of warming yang and transforming fluid, strengthening the spleen, and alleviating dampness. It is primarily used to treat chest and side fullness, dizziness, palpitations, short temper, coughing, slippery tongue coating, slippery or deep and tight pulse, and phlegm and fluid due to central yang deficiency. In clinical practice, it is widely used to treat symptoms in which water stagnates in the central burner, such as chronic bronchitis, bronchial asthma, cardiogenic edema, edema due to chronic glomerulonephritis, Meniere's disease, and neurosis.

[0003] In the prescription for Licorice, Guizhou, and Zhizhou Decoction, Poria (Poria cocos) is used to promote diuresis, relieve dampness, strengthen the spleen, and calm the heart. It mainly contains the beta-polysaccharide pachyman, which accounts for about 93% of its dry weight, as well as buprenorphine, protein, fat, lecithin, choline, histidine, ergosterol, etc., of which the polysaccharide pachyman is sparingly soluble in water, while the other components are soluble in water. Cinnamon Bark (Cinnamon Bark) is used to induce sweating, clear muscles, warm the meridians, stimulate yang qi, and balance and lower qi. It mainly contains volatile oils, mainly consisting of cinnamal aldehyde, as well as phenols, organic acids, polysaccharides, glycosides, coumarone essence, and tannins, among which the volatile oils are the basis for the sweating and warm the meridians, while the other components are water-soluble. White Atractylodes Rhizome (Byakkushou) is used to strengthen the spleen and strengthen qi. It has the functions of drying, dampening, hydrating, stopping sweating, and easing pregnancy. It mainly contains volatile oils whose main components are atractylone, atractylodin, atractyl ether, juniper camphor, and atractylenolide, as well as fructose, inosin, Atractylodes Root polysaccharides, several amino acids, and vitamin A compounds, among which volatile oils are the main substance basis for the drying, dampening, and hydrating functions, and the other components are soluble in water. Licorice (Glycyrrhiza Root) has the functions of toning the spleen and invigorating qi, clearing heat and detoxifying, expectorating and stopping coughs, relieving pain, and harmonizing various things. It mainly contains triterpenoids (potassium and calcium salts of triterpenoid glycyrrhizinic acid are glycyrrhizin, the sweet component of licorice), flavonoids, alkaloids, polysaccharides, etc., all of which are soluble in water.

[0004] Traditionally, Licorice, Cinnamon, and Atractylodesma Decoction is mostly prepared as a decoction, which is inconvenient to use. Granules and traditional decoctions are closest to the dosage form and are convenient to carry and take, making them one of the important dosage forms of current traditional Chinese medicine compound preparations. Granules are mainly divided into two types: wet granulation and dry granulation. Dry granulation technology can be achieved using a roller flat granulator. A traditional Chinese medicine extract with a certain relative density is spray-dried to obtain a dried extract powder. After adding certain additives, the powder is pressed into a sheet using a dry extrusion granulator and then pulverized into granules. This method requires fewer additives and is advantageous in improving the stability, disintegration, and dissolution properties of the granules. However, the dried extract obtained by spray drying is highly hygroscopic.

[0005] Therefore, it is important to modify the product using appropriate additives, which must not only have a certain adhesive property but also be resistant to moisture absorption. High fluidity directly affects the difficulty of processing. Hygroscopicity and fluidity are important physical properties that affect the molding process of herbal medicine preparations and intermediates (e.g., extracts, granules) and the quality stability of the formulated product. Therefore, how to reduce the hygroscopicity of Rikkeijutsukanto extract and improve its fluidity is an important means of improving the convenience and stability of subsequent processing of Rikkeijutsukanto.

[0006] The present invention adopts a single-factor test, and uses the angle of repose, moisture absorption rate, and compressibility as indicators to determine the type of modifier, modifier ratio, and modification method used to prepare the modified product, and screens the manufacturing process of the modified product, thereby improving the moisture-proof performance and direct pressing performance of the Rikkyoto Atractylodes Macrocephala Gum Tang extract powder, and effectively improving the subsequent formulation process of Rikkyoto Atractylodes Macrocephala Gum Tang. Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention aims to provide a Rikkyoto Atractylodes Rhizome Extract and a method for producing the same, which improves the moisture-proofing and direct pressing performance of the Rikkyoto Atractylodes Rhizome Extract powder by screening the type, ratio and modification method of the modifier. [Means for solving the problem]

[0008] In order to achieve the above object, the present invention provides the following.

[0009] In one aspect, the present invention provides a Rikkyotokanto extract comprising an additive consisting of maltodextrin and finely powdered silica gel, and Rikkyotokanto extract powder, wherein the modification ratio of extract powder:maltodextrin:finely powdered silica gel is 64-74:25-39:1.

[0010] Preferably, the modified ratio of the extract powder: the maltodextrin: the finely powdered silica gel is 64:35:1 or 74:25:1, and most preferably 64:35:1.

[0011] In another aspect, the present invention provides a method for producing a pharmaceutical composition comprising: 1) Extraction step: extracting raw materials consisting of Poria cocos, Cinnamon bark, Atractylodes atractylodes and Licorice root with water to obtain an extract; 2) Concentration step: A step of filtering, separating, and concentrating the extract to obtain a concentrate; 3) Drying step: A step of spray-drying the concentrated liquid to obtain extract powder; 4) Denaturation step: The extract powder is denatured with maltodextrin and fine silica gel powder by low-temperature ultrafine grinding using a vibration method. The present invention provides a method for producing a Ryokukeijutsukanto extract, which comprises:

[0012] Preferably, the raw materials in step 1) are 4 parts Poria cocos, 3 parts Cinnamon bark, 3 parts White Atractylodes Root, and 2 parts Licorice.

[0013] Preferably, the specific parameters of the extraction in step 1) are an 8- to 12-fold water addition amount and an extraction time of 1 to 3 hours, and more preferably, the specific parameters of the extraction in step 1) are a 10-fold water addition amount and an extraction time of 2 hours.

[0014] Preferably, the concentrated liquid in step 2) has a density of 1.10 to 1.15, and more preferably, the concentrated liquid in step 2) has a density of 1.10.

[0015] Preferably, the specific parameters of the denaturing method in step 4) are a media filling rate of 75 to 85%, an amplitude of 5 to 6 mm, and a temperature of -10 to 0°C; more preferably, the specific parameters of the denaturing method in step 4) are a media filling rate of 80%, an amplitude of 5.5 mm, and a temperature of -2°C.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] Hygroscopicity and fluidity are important physical properties that affect the molding process of herbal medicine preparations and intermediates (e.g., extracts, granules), as well as the quality stability of the preparation products. The present invention adopts single-factor testing to use the angle of repose, moisture absorption rate, and compressibility as indicators to determine the type of modifier, modifier ratio, and modification method used to prepare the modified product. The manufacturing process for screening the modified product improves the moisture-proof performance and direct pressing performance of the Licorice Ceruleum Decoction extract powder, and has the effect of effectively improving the subsequent formulation process of Licorice Ceruleum Decoction. [Brief explanation of the drawings]

[0018] [Figure 1] 1 is a graph showing the change over time in moisture absorption rate for a control example, Example 1, and Comparative Examples 1 to 5. [Figure 2] The bulk density, tap density, compressibility and angle of repose of the control example, Example 1 and Comparative Examples 1 to 5. [Figure 3] 1 is a graph showing the change over time in moisture absorption rate for a control example, examples 1 and 2, and comparative example 6. [Figure 4] 1 shows the bulk density, tap density, compressibility and angle of repose of Examples 1 and 2 and Comparative Example 6. [Figure 5] 1 is a graph showing the change over time in moisture absorption rate for a control example, Example 1, and Comparative Examples 7 to 9. [Figure 6] 1 shows the bulk density, tap density, compressibility and angle of repose of Example 1 and Comparative Examples 7 to 9. [Figure 7] 1 is a graph showing the change over time in moisture absorption rate for a control example, Example 1, and Comparative Examples 10 to 11. [Figure 8] 1 shows the bulk density, tap density, compressibility and angle of repose of Example 1 and Comparative Examples 10 and 11. DETAILED DESCRIPTION OF THE INVENTION

[0019] In order to facilitate understanding of the technical means, creative features, objectives, and effects of the present invention, the present invention will be further described below with specific examples. However, the following examples are merely preferred examples of the present invention and are not exhaustive. Any other examples that can be obtained by a person skilled in the art based on the examples in the embodiments without any creative effort fall within the scope of the present invention. Furthermore, all raw materials used in the present invention are common commercially available products, and their origins are not particularly limited. Technical and scientific terms used in the examples have meanings that are commonly understood by those skilled in the art to which the present invention belongs.

[0020] The present invention adopts a single-factor test, and uses the angle of repose, moisture absorption rate, and compressibility as indicators to examine the type of modifier, modifier ratio, and modification method used to prepare the modified product, and screen the manufacturing process of the modified product to improve the moisture-proof performance and direct press performance of the Licorice Ceruleum Glycerin Decoction extract powder.

[0021] Indicator measurement method: (1) Moisture absorption rate An appropriate amount of test sample was placed in a constant weight weighing bottle and dehumidified in a dryer for 48 hours. Then, the sample was removed and precisely weighed. The sample was then placed in a supersaturated sodium chloride solution at 25°C and a relative humidity of 75%. The sample was then removed and weighed at 2, 4, 8, 12, 24, 48, 72, and 96 hours, and the moisture absorption rate was calculated. Moisture absorption rate = (weight after moisture absorption - weight before moisture absorption) / weight before moisture absorption x 100%

[0022] (2)Angle of repose Using the GTB powder flowability measuring device, the powder flows uniformly through a funnel with a lower opening of 10 mm and forms a cone on the stage. After the powder forms a stable and symmetrical cone, the supply is stopped and the device automatically reads the data.

[0023] (3) Compression degree The mass (M0) of a 25 mL graduated cylinder is precisely weighed, and the powder is poured evenly into the graduated cylinder through a funnel of a certain height. When the volume reaches 25 mL, the total mass (M1) of the powder and the graduated cylinder is precisely weighed to determine the bulk density (BD). After vibrating at a speed of 120 rpm for 3 minutes, the volume (V) of the powder after tapping is read to determine the tapped density (TD). The compressibility (C) is then calculated. Compression degree (C) = (TD-BD) / TD x 100%

[0024] Control example 1) Extraction: Weigh out the ingredients in the prescribed proportions of 4 parts Poria cocos, 3 parts Cinnamon bark, 3 parts Atractylodes abies, and 2 parts Licorice, place them in an extraction basket, add 10 times the amount of water, and brew once. The extraction time is 2 hours.

[0025] 2) Concentration: The extract was filtered, separated, and concentrated to a density of 1.0 (60°C) to obtain a concentrated solution.

[0026] 3) Drying: The concentrate is spray dried to obtain the extract powder, which is ready for use.

[0027] The sample was sieved through an 80 mesh sieve and labeled as a control, and then sampled to measure each index.

[0028] Example 1 1) Extraction: Weigh out the ingredients in the prescribed proportions of 4 parts Poria cocos, 3 parts Cinnamon bark, 3 parts Atractylodes abies, and 2 parts Licorice, place them in an extraction basket, add 10 times the amount of water, and brew once. The extraction time is 2 hours.

[0029] 2) Concentration: The extract was filtered, separated, and concentrated to a density of 1.0 (60°C) to obtain a concentrated solution.

[0030] 3) Drying: The concentrate is spray dried to obtain the extract powder, which is ready for use.

[0031] 4) Modification: Weigh out Ryokeijutsukanto extract powder, maltodextrin, and fine silica gel in a ratio of 64:35:1, and mix them in a grinder for 6 minutes at a media filling rate of 80%, amplitude of 5.5 mm, and temperature of -2°C. When the mixture of extract powder and additives became uniform in color, the modified product was obtained, and samples were taken to detect each indicator.

[0032] Example 2 In step 4) of Example 1, the denaturation ratio was changed to 74:25:1, but a denatured product was obtained in the same manner as in Example 1, and samples were taken to detect each indicator.

[0033] Comparative Example 1 1) Extraction: Weigh out the ingredients in the prescribed proportions of 4 parts Poria cocos, 3 parts Cinnamon bark, 3 parts Atractylodes abies, and 2 parts Licorice, place them in an extraction basket, add 10 times the amount of water, and brew once. The extraction time is 2 hours.

[0034] 2) Concentration: The extract was filtered, separated, and concentrated to a density of 1.0 (60°C) to obtain a concentrated solution.

[0035] 3) Drying: The concentrate is spray dried to obtain the extract powder, which is ready for use.

[0036] 4) Modification: Weigh out the Ryokeijutsukanto extract powder and microcrystalline cellulose in a ratio of 6:4, and mix them in a grinder for 6 minutes at a media filling rate of 80%, amplitude of 5.5 mm, and temperature of -2°C. When the mixture of extract powder and additives became uniform in color, the modified product was obtained, sampled, and each index was detected.

[0037] Comparative Example 2 The same procedure was carried out as in Comparative Example 1, except that in step 4), microcrystalline cellulose was replaced with lactose.

[0038] Comparative Example 3 The same procedure was carried out as in Comparative Example 1, except that in step 4), microcrystalline cellulose was replaced with soluble starch.

[0039] Comparative Example 4 The same procedure was carried out as in Comparative Example 1, except that in step 4), microcrystalline cellulose was replaced with maltodextrin.

[0040] Comparative Example 5 The same procedure was carried out as in Comparative Example 1, except that in step 4), microcrystalline cellulose was replaced with finely powdered silica gel.

[0041] Comparative Example 6 In Example 1, in step 4), the modification ratio was changed to 54:45:1, and a modified product was obtained in the same manner, sampled, and each indicator was detected.

[0042] Comparative Example 7 In Example 1, in step 4), the extract of Atractylodes Rhizome Gum Tang (based on the extract powder yield), maltodextrin, and fine silica gel were weighed in a ratio of (64:35:1), and water was added to prepare a mixture with a relative density of approximately 1.10 (60°C). The mixture was then spray-dried to obtain a spray-dried powder, which was then used to obtain a modified product. Samples were then taken to detect each indicator, and the same procedures were carried out.

[0043] Comparative Example 8 In Example 1, in step 4), the extract of Atractylodes Rhizome Gum Tang (based on the extract powder yield), maltodextrin, and fine silica gel were weighed in a ratio of (64:35:1), and water was added at room temperature to prepare a mixture with a relative density of approximately 1.12 (25°C). After belt vacuum drying, a dry powder was obtained by filtering through a 60 mesh filter to obtain a denatured product, which was then sampled and each indicator was detected.

[0044] Comparative Example 9 In Example 1, in step 4), the extract powder of Rikkyotokanto, maltodextrin and fine silica gel were weighed in a ratio of (64:35:1) and mixed by simple stirring. When the mixture of the extract powder and additives became uniform in color, a modified product was obtained, which was then sampled and each indicator was detected.

[0045] Comparative Example 10 The same procedure was carried out as in Example 1, except that in step 4) maltodextrin was replaced with lactose.

[0046] Comparative Example 11 The same procedure was carried out as in Example 1, except that in step 4), maltodextrin was replaced with microcrystalline cellulose.

[0047] As can be seen from the results in Figures 1 and 2 and Figures 7 and 8, after the Licorice, Cinnamon, and Licorice Gum Decoction extract was modified with each additive, the moisture absorption rate decreased to different degrees, and the powder properties such as the angle of repose and compressibility changed to different degrees. Among them, the angle of repose was the lowest in the case of finely powdered silica gel, and the compressibility was the lowest in the case of maltodextrin. The effect of combining maltodextrin and finely powdered silica gel was clearly superior to that of a single additive or a combination with other additives.

[0048] As can be seen from the results in Figures 3 and 4, after the Licorice, Cinnamon, and Licorice Gum Decoction extract is modified with additives in different ratios, the moisture absorption rate decreases, but the difference is not significant, and the difference in compressibility and density is not significant. Among them, the angle of repose of two ratios of extract powder, maltodextrin, and fine silica gel (64:35:1, 74:25:1) is less than 40° and has good fluidity. When the angle of repose is less than 40°, the fluidity of the powder at this time is suitable for subsequent formulation. Among them, the appropriate ratio of additive amounts is 64:35:1, which is the optimal mixing ratio.

[0049] As can be seen from the results of Figures 5 and 6, after the Rikkyoto Atractylodes Rhizome Decoction extract was modified in different ways, the moisture absorption rates all decreased, and Example 1 and Comparative Example 7 were smaller than Comparative Examples 8 and 9. Except for Comparative Example 8, there was no significant difference in the compressibility, density, and angle of repose. Example 1 had smaller angle of repose, compressibility, and moisture absorption rate, and better fluidity and moisture resistance, i.e., the properties of the modified product obtained by mixing the Rikkyoto Atractylodes Rhizome Decoction extract by vibration-type low-temperature ultrafine grinding were better.

[0050] Hygroscopicity and fluidity are important physical properties that affect the molding process of herbal medicine preparations and intermediates (e.g., extracts, granules) and the quality stability of the formulation products. Generally, the bulk density and angle of repose of a powder directly affect the fluidity of the material during the pressing process, and the degree of compression directly reflects the fluidity of the powder. The smaller the angle of repose and degree of compression, the better the powder's fluidity. Reducing the hygroscopicity of herbal medicine extract powder and improving its fluidity are necessary measures to ensure the quality stability of the subsequent formulation. The present invention provides a method for improving the fluidity, compressibility, and hygroscopicity of Licorice, Gui, Zhu, and Zhu extract powder, which has the effect of effectively improving the subsequent formulation process of Licorice, Gui, Zhu, and Zhu extract.

[0051] Finally, it should be noted that the above content is only for explaining the technical solution of the present invention, and does not limit the scope of the claims of the present invention. Any simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention will not deviate from the substance and scope of the technical solution of the present invention.

Claims

1. The Ryokukeijutsukanto extract comprises an additive consisting of maltodextrin and finely powdered silica gel, and Ryokukeijutsukanto extract powder, and is characterized in that the modified ratio of extract powder:maltodextrin:finely powdered silica gel is 64-74:25-39:

1.

2. The extract of Rikkyotokanto described in claim 1, characterized in that the modified ratio of the extract powder: the maltodextrin: the finely powdered silica gel is 64:35:1 or 74:25:

1.

3. 1) Extraction step: extracting raw materials consisting of Poria cocos, Cinnamon bark, Atractylodes abies and Licorice root with water to obtain an extract; 2) Concentration step: filtering, separating, and concentrating the extract to obtain a concentrate; 3) Drying step: A step of spray-drying the concentrated liquid to obtain an extract powder; 4) Denaturation step: The extract powder is denatured with maltodextrin and fine silica gel powder by vibratory low-temperature ultrafine grinding. A method for producing a Ryokukeijutsukanto extract, comprising:

4. 4. The method for producing a Licorice-Guaishu-Kanto extract according to claim 3, characterized in that the raw materials in step 1) are 4 parts of Poria Cocos, 3 parts of Cinnamon Bark, 3 parts of Atractylodes Rhizome, and 2 parts of Licorice Root.

5. The method for producing the extract of Licorice, Cinnamon, and Glycerin Decoction described in claim 3, characterized in that the specific parameters of the extraction in step 1) are: the amount of water added is 8 to 12 times, and the extraction time is 1 to 3 hours.

6. The method for producing the extract of Licorice, Cinnamon, and Glycerin Decoction described in claim 5, characterized in that the specific parameters of the extraction in step 1) are: 10 times the amount of water added and 2 hours of extraction time.

7. The method for producing the extract of Atractylodes Rhizome Gan Tang described in claim 3, characterized in that the density of the concentrated liquid in step 2) is 1.10 to 1.

15.

8. The method for producing the extract of Atractylodes Rhizome Gan Tang described in claim 7, wherein the density of the concentrated liquid in step 2) is 1.

10.

9. The method for producing the Licorice, Cinnamon, and Glycerin Decoction extract described in claim 3, characterized in that the specific parameters of the denaturation method in step 4) are: media filling rate of 75% to 85%, amplitude of 5 to 6 mm, and temperature of -10°C to 0°C.

10. The method for producing Licorice, Cinnamon, and Glycerin Decoction extract, as described in claim 7, characterized in that the specific parameters of the denaturation method in step 4) are: media filling rate 80%, amplitude 5.5 mm, and temperature -2°C.

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