Preparation method of angelica sinensis blood replenishing granules

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a preparation method of angelica sinensis blood replenishing granules. Comprising the following steps: (1) adding water into wine radix angelicae sinensis to moisten the wine radix angelicae sinensis, extracting volatile oil by adopting a steam straight-through method, and collecting the volatile oil and medicine residues; (2) clathrating the volatile oil, beta-cyclodextrin and water, drying and crushing to obtain a volatile oil clathrate compound; (3) mixing the medicine residues with astragalus membranaceus, adding water, performing reflux extraction to obtain an extracting solution, and performing vacuum concentration to obtain a concentrated solution; (4) adding maltodextrin into the concentrated solution, uniformly mixing, sieving, and carrying out spray drying to obtain extract powder; and (5) adding auxiliary materials and a volatile oil clathrate compound into the extract powder, uniformly mixing, and performing dry granulation to obtain the angelica sinensis blood replenishing granules. By optimizing the preparation process, the ferulic acid component in wine angelica sinensis is greatly reserved, the high content of volatile oil is ensured, and the prepared angelica sinensis blood replenishing granules are similar to a reference sample.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a preparation method of angelica blood-enriching granules. Background Art

[0002] Volatile oil, also known as essential oil, is a general term for a class of oily liquids in plants that are volatile, can be distilled with water vapor and are insoluble in water. Research on volatile oils is currently an important part of the research on compound preparations of ancient classic prescriptions. In order to restore "a bowl of soup", the top priority of the research is to retain the volatile oils and keep the preparations consistent with the benchmark samples. Therefore, how to add volatile oils to the preparations and retain them for a long time is a key point, while at the same time streamlining the auxiliary materials without affecting the quality of the preparations and clinical efficacy.

[0003] Danggui Buxue Tang comes from Li Dongyuan's "Discussion on Internal and External Injuries" in the Jin Dynasty, which is included in the "Ancient Catalog (First Batch)" published in April 2018. Chinese invention patent CN114632064A discloses a method for preparing Danggui Buxue Tang granules, in which maltodextrin is added to the concentrate, and the extract powder is spray-dried to obtain extract powder, and microcrystalline cellulose, soluble starch and magnesium stearate are added to the extract powder, and dry granulation is performed after mixing. In this method, due to the excessive addition of auxiliary materials, the final granule preparation is too different from the classic prescription. Chinese invention patent CN110801477A discloses a method for preparing hemostatic and menstruation regulating granules, which proposes to mix Danggui and Buddha's hand, extract by distillation, collect volatile oil, and encapsulate it with β-cyclodextrin, but the ability of distillation extraction to collect volatile oil is less efficient than the steam direct method, which will lead to a large loss of ferulic acid components in wine Danggui, affecting the medicinal value. Summary of the invention

[0004] The purpose of the present invention is to provide a preparation method of Angelicae Sinensis Blood-Replenishing Granules. By optimizing the preparation process, the ferulic acid component in Angelicae Sinensis wine is greatly retained, the high content of volatile oil is guaranteed, and the prepared Angelicae Sinensis Blood-Replenishing Granules are similar to the benchmark sample.

[0005] The present invention is achieved through the following technical solutions: The preparation method of the Danggui Buxue Granules of the present invention comprises the following steps: (1) adding water to the wine-prepared angelica sinensis to moisten it, extracting volatile oil by steam direct-flow method, and collecting volatile oil and dregs; (2) Inclusion compounding the volatile oil obtained in step (1) with β-cyclodextrin and water, drying and then crushing to obtain a volatile oil inclusion compound; (3) mixing the medicinal residue obtained in step (1) with Astragalus, adding water for reflux extraction, obtaining an extract, and concentrating under reduced pressure to obtain a concentrated solution; (4) Add maltodextrin to the concentrated solution and mix evenly, sieve and spray dry to obtain extract powder; (5) Adding auxiliary materials and the volatile oil inclusion compound obtained in step (2) to the extract powder, mixing well and then dry granulating to obtain the Angelica Blood-Replenishing Granules.

[0006] Preferably, in step (1), the amount of water added is 10-20% of the mass of the wine angelica; when the volatile oil is extracted by the steam direct method, the steam flow rate is 60-70 kg / h, and the extraction time is 2-3 h.

[0007] Preferably, in step (2), the mass ratio of volatile oil, β-cyclodextrin and water is 1:8~10:80~100; the drying temperature is 30~40°C; the inclusion process is specifically: adding water to the colloid mill, starting the circulation, then adding β-cyclodextrin, after sufficient mixing, dripping the volatile oil into the colloid mill and mixing, and the inclusion is completed.

[0008] Preferably, in step (3), the mass ratio of astragalus to angelica wine is 5:1; during reflux extraction, the amount of water added is 9 to 10 times the total mass of astragalus and angelica wine, and the extraction time is 60 to 70 minutes; the temperature of reduced pressure concentration is 60 to 70°C, and the density of the concentrated solution is 1.05 to 1.10 g / cm 3 .

[0009] Preferably, in step (4), the amount of maltodextrin added is 4-5% of the total mass of astragalus and angelica sinensis; and the mesh size of the sieve is 80-100 mesh.

[0010] Preferably, in step (5), the mass ratio of the total amount of astragalus and angelica wine to the final angelica blood-replenishing granules is 2.48:1, and the auxiliary material is maltodextrin.

[0011] Compared with the prior art, the present invention has the following beneficial effects: 1. The present invention adopts the steam direct method to extract the volatile oil, so that the volatile oil can be better extracted and collected. Cyclodextrin can be used to prepare inclusion compounds of various drug molecules, which mainly play the role of improving dissolution and bioavailability, which can be attributed to the increase in solubility and the improvement of chemical and physical stability. The inclusion compound of cyclodextrin is also used to cover the bad taste of active substances and convert liquid substances into solid materials. β-cyclodextrin has poor solubility and is non-toxic for oral administration. It is mainly used for tablets and capsules. In the present invention, the characteristics of β-cyclodextrin are utilized to mix it with volatile oil to form a solid inclusion compound, which is added to the granules, which can effectively preserve the volatile oil components, avoid the loss of volatile oil, and ensure the content of volatile oil in Danggui Buxue Granules.

[0012] 2. The present invention optimizes the preparation process and the amount of auxiliary materials, and adds a certain amount of maltodextrin during spray drying. Maltodextrin is also called water-soluble dextrin or enzymatic dextrin, which has the characteristics of low sweetness, no peculiar smell, easy digestion, good solubility, low fermentability, good filling effect, not easy to absorb moisture, strong thickening, good carrier properties, good stability, and difficult to deteriorate. It is often used in traditional Chinese medicine preparations. In the present invention, adding maltodextrin before dry granulation can improve the situation of spray drying sticking to the tower and improve the fluidity of the powder. At the same time, the amount and type of auxiliary materials are reduced, and volatile oil is added to the preparation to make it closer to the benchmark sample. DETAILED DESCRIPTION

[0013] The present invention is further described below with reference to the examples. If no specific conditions are specified in the examples, the experiments are carried out according to conventional conditions or conditions recommended by the manufacturer. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0014] Example 1 The preparation method of the Danggui Buxue Granules comprises the following steps: (1) adding water to the wine-prepared angelica sinensis to moisten it, extracting volatile oil by steam direct-flow method, and collecting volatile oil and dregs; The mass of the wine-boiled angelica is 413 g, and the amount of water added is 15% of the mass of the wine-boiled angelica; when the volatile oil is extracted by the steam direct method, the steam flow rate is 65 kg / h and the extraction time is 2.5 h.

[0015] (2) Inclusion compounding the volatile oil obtained in step (1) with β-cyclodextrin and water, drying and then crushing to obtain a volatile oil inclusion compound; The mass ratio of volatile oil, β-cyclodextrin and water is 1:9:90; the drying temperature is 35°C; The specific inclusion process is as follows: add water to the colloid mill, start the circulation, add β-cyclodextrin, mix thoroughly, drop volatile oil into the colloid mill and mix, and the inclusion is completed.

[0016] (3) mixing the medicinal residue obtained in step (1) with Astragalus, adding water for reflux extraction, obtaining an extract, and concentrating under reduced pressure to obtain a concentrated solution; The mass ratio of Astragalus to Angelica sinensis wine was 5:1. During reflux extraction, the amount of water added was 9.5 times the total mass of Astragalus and Angelica sinensis wine, and the extraction time was 65 min. The temperature of vacuum concentration was 65 ° C, and the density of the concentrate was 1.10 g / cm 3 .

[0017] (4) Add maltodextrin to the concentrated solution and mix evenly, sieve and spray dry to obtain extract powder; The amount of maltodextrin added is 4.5% of the total mass of astragalus and angelica wine; the mesh number of the sieve is 90 meshes.

[0018] (5) adding auxiliary material maltodextrin and the volatile oil inclusion compound obtained in step (2) to the extract powder, mixing well and then dry granulating to obtain 50 bags of the Danggui Buxue Granules; The mass ratio of the total amount of astragalus and wine-made angelica to the final angelica blood-replenishing granules is 2.48:1.

[0019] Example 2 The preparation method of the Danggui Buxue Granules comprises the following steps: (1) adding water to the wine-prepared angelica sinensis to moisten it, extracting volatile oil by steam direct-flow method, and collecting volatile oil and dregs; The mass of the wine-boiled angelica is 3717 g, and the amount of water added is 10% of the mass of the wine-boiled angelica; when the volatile oil is extracted by the steam direct method, the steam flow rate is 60 kg / h and the extraction time is 3 h.

[0020] (2) Inclusion compounding the volatile oil obtained in step (1) with β-cyclodextrin and water, drying and then crushing to obtain a volatile oil inclusion compound; The mass ratio of volatile oil, β-cyclodextrin and water is 1:8:80; the drying temperature is 30°C; The specific inclusion process is as follows: add water to the colloid mill, start the circulation, add β-cyclodextrin, mix thoroughly, drop volatile oil into the colloid mill and mix, and the inclusion is completed.

[0021] (3) mixing the medicinal residue obtained in step (1) with Astragalus, adding water for reflux extraction, obtaining an extract, and concentrating under reduced pressure to obtain a concentrated solution; The mass ratio of Astragalus to Angelica sinensis wine was 5:1. During reflux extraction, the amount of water added was 9 times the total mass of Astragalus and Angelica sinensis wine, and the extraction time was 60 min. The temperature of vacuum concentration was 60 ° C, and the density of the concentrate was 1.05 g / cm 3 .

[0022] (4) Add maltodextrin to the concentrated solution and mix evenly, sieve and spray dry to obtain extract powder; The amount of maltodextrin added is 4% of the total mass of astragalus and angelica sinensis; the mesh number of the sieve is 80 meshes.

[0023] (5) adding maltodextrin as an auxiliary material and the volatile oil inclusion compound obtained in step (2) to the extract powder, mixing well and then dry granulating to obtain 450 bags of the Danggui Buxue Granules; The mass ratio of the total amount of astragalus and wine-made angelica to the final angelica blood-replenishing granules is 2.48:1.

[0024] Example 3 The preparation method of the Danggui Buxue Granules comprises the following steps: (1) adding water to the wine-prepared angelica sinensis to moisten it, extracting volatile oil by steam direct-flow method, and collecting volatile oil and dregs; The mass of the wine-boiled angelica is 413 g, and the amount of water added is 20% of the mass of the wine-boiled angelica; when the volatile oil is extracted by the steam direct method, the steam flow rate is 70 kg / h and the extraction time is 2 h.

[0025] (2) Inclusion compounding the volatile oil obtained in step (1) with β-cyclodextrin and water, drying and then crushing to obtain a volatile oil inclusion compound; The mass ratio of volatile oil, β-cyclodextrin and water is 1:10:100; the drying temperature is 40°C; The specific inclusion process is as follows: add water to the colloid mill, start the circulation, add β-cyclodextrin, mix thoroughly, drop volatile oil into the colloid mill and mix, and the inclusion is completed.

[0026] (3) mixing the medicinal residue obtained in step (1) with Astragalus, adding water for reflux extraction, obtaining an extract, and concentrating under reduced pressure to obtain a concentrated solution; The mass ratio of Astragalus to Angelica sinensis wine was 5:1. During reflux extraction, the amount of water added was 10 times the total mass of Astragalus and Angelica sinensis wine, and the extraction time was 70 min. The temperature of vacuum concentration was 70 ° C, and the density of the concentrate was 1.10 g / cm 3 .

[0027] (4) Add maltodextrin to the concentrated solution and mix evenly, sieve and spray dry to obtain extract powder; The amount of maltodextrin added is 5% of the total mass of astragalus and wine angelica; the mesh number of the sieve is 100 meshes.

[0028] (5) adding auxiliary material maltodextrin and the volatile oil inclusion compound obtained in step (2) to the extract powder, mixing well and then dry granulating to obtain 50 bags of the Danggui Buxue Granules; The mass ratio of the total amount of astragalus and wine-made angelica to the final angelica blood-replenishing granules is 2.48:1.

[0029] Comparative Example 1 Refer to Example 1, except that in step (1), the volatile oil is extracted by distillation. The specific operation is: add water twice the mass of angelica sinensis to the angelica sinensis, and the extraction time is 4 hours. Due to the low yield of volatile oil, the aromatic water is collected together and the inclusion of step (2) is carried out.

[0030] Comparative Example 2 Refer to Example 2, except that, in step (5): auxiliary materials and volatile oil inclusion compound are added to the extract powder, mixed and dry granulated to obtain Angelica Blood-Replenishing Granules, wherein the auxiliary materials are 2175 g of microcrystalline cellulose, 2900 g of soluble starch and 72.5 g of magnesium stearate.

[0031] Comparative Example 3 Refer to Example 3, except that in step (4), dextrin is added to the concentrated solution, and in step (5), the auxiliary material added is dextrin.

[0032] Comparative Example 4 Refer to Example 3, except that in step (4), soluble starch is added to the concentrated solution, and in step (5), the auxiliary material added is soluble starch.

[0033] The preparation processes of Examples 1 to 3 and Comparative Examples 1 to 4 were monitored, with attention paid to the theoretical paste yield, actual paste yield, spray drying state, extract powder yield, moisture content, and particle yield indicators. The results are shown in Table 1.

[0034] Table 1 Monitoring results of the preparation process of Danggui Buxue Granules

[0035] As can be seen from Table 1, the process parameters of the preparation of Angelica Blood-enriching Granules in Examples 1 to 3 are relatively stable, the theoretical paste yield is close to the actual paste yield, the amount of water added increases, the paste yield increases, the spray drying is in good condition, does not stick to the tower, does not stick to the barrel, has good fluidity during dry granulation, and the granule yield is relatively stable. Comparative Example 1 uses the distillation oil extraction method, which leads to a lower volatile oil yield, an increased aromatic water yield, a large proportion of aromatic water during inclusion, and a prolonged inclusion drying time; Comparative Example 2 has a large amount of auxiliary materials added during dry granulation, resulting in a small proportion of effective ingredients, and the granule dosage is too large per serving, which does not meet the requirements of the research and development of classic prescriptions; the granules of Comparative Examples 3 and 4 use dextrin and soluble starch as auxiliary materials, respectively, resulting in a large difference between the theoretical paste yield and the actual paste yield, the spray powder slightly sticks to the tower during spray drying, the fluidity is poor during dry granulation, and the granule yield is low.

[0036] The angles of repose of the extract powders and granules of Examples 1 to 3 and Comparative Examples 1 to 4 were investigated, and the results are shown in Table 2. Table 2 Results of the angle of repose of extract powder and granules

[0037] As can be seen from Table 2, maltodextrin is added when preparing the extract powder in Examples 1 to 3 and Comparative Examples 1 to 2, so that the extract powder has better fluidity, and the angle of repose is <40°, which is lower than that of Comparative Examples 3 and 4. The granules prepared by adding maltodextrin as an auxiliary material during dry granulation in Examples 1 to 3 and Comparative Example 1 have better fluidity, and the angle of repose is <40°; the granules prepared by adding microcrystalline cellulose, soluble starch, and magnesium stearate during dry granulation in Comparative Example 2 have the best fluidity, but the proportion of auxiliary materials is too large, resulting in an increase in the dosage, which does not meet the requirements of the research and development of classic prescriptions; the granules prepared by Comparative Examples 3 to 4 using dextrin and soluble starch as auxiliary materials respectively have poor fluidity, and the angle of repose is >40°, which is not conducive to improving production efficiency.

[0038] The contents of astragaloside IV, ferulic acid and ligustilide in the Danggui Buxue Granules prepared in Examples 1 to 3 and Comparative Examples 1 to 4 were tested, and the results are shown in Table 3.

[0039] Table 3 Data on the content of astragaloside Ⅳ, ferulic acid and ligustilide

[0040] As can be seen from Table 3, the content determination results of the Danggui Buxue Granules prepared in Examples 1 to 3 all meet the internal control indicators of the variety; Comparative Example 1 uses distillation to extract volatile oil, resulting in a decrease in the ferulic acid content, which is lower than the internal control indicator, and aromatic water is added during inclusion, resulting in a high content of ligustilide, which meets the internal control indicator; Comparative Example 2 adds a large amount of auxiliary materials during spray drying and dry granulation, resulting in a finished product rate higher than the established target, while the contents of various indicators are lower than the internal control indicators.

Claims

1. A method for preparing Danggui Buxue Granules, characterized by: The following steps are involved: (1) adding water to the wine-prepared angelica sinensis to moisten it, extracting volatile oil by steam direct-flow method, and collecting volatile oil and dregs; (2) Inclusion compounding the volatile oil obtained in step (1) with β-cyclodextrin and water, drying and then crushing to obtain a volatile oil inclusion compound; (3) mixing the medicinal residue obtained in step (1) with Astragalus, adding water for reflux extraction, obtaining an extract, and concentrating under reduced pressure to obtain a concentrated solution; (4) Add maltodextrin to the concentrated solution and mix evenly, sieve and spray dry to obtain extract powder; (5) Adding auxiliary material maltodextrin and the volatile oil inclusion compound obtained in step (2) to the extract powder, mixing well and then dry granulating to obtain the Angelica Blood-Replenishing Granules.

2. The method for preparing the Danggui Buxue Granule according to claim 1, characterized in that: In step (1), the amount of water added is 10-20% of the weight of the wine angelica.

3. The method for preparing the Danggui Buxue Granule according to claim 2, characterized in that: In step (1), when the volatile oil is extracted by the steam direct method, the steam flow rate is 60-70 kg / h and the extraction time is 2-3 h.

4. The method for preparing the Danggui Buxue Granule according to claim 1, characterized in that: In step (2), the mass ratio of volatile oil, β-cyclodextrin and water is 1:8~10:80~100.

5. The method for preparing the Danggui Buxue Granule according to claim 1, characterized in that: In step (3), the mass ratio of astragalus to wine angelica is 5:

1.

6. The method for preparing the Danggui Buxue Granules according to claim 5, characterized in that: In step (3), during reflux extraction, the amount of water added is 9 to 10 times the total mass of the astragalus and the wine-boiled angelica, and the extraction time is 60 to 70 minutes.

7. The method for preparing the Danggui Buxue Granules according to claim 6, characterized in that: In step (3), the temperature of the reduced pressure concentration is 60-70°C, and the density of the concentrated solution is 1.05-1.10 g / cm 3 .

8. The method for preparing the Danggui Buxue Granule according to claim 1, characterized in that: In step (4), the amount of maltodextrin added is 4-5% of the total mass of astragalus and angelica wine.

9. The method for preparing the Danggui Buxue Granule according to claim 1, characterized in that: In step (5), the mass ratio of the total amount of astragalus and angelica wine to the final angelica blood-replenishing granules is 2.48:1.

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