Double-orange granules and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to double-orange granules and a preparation method thereof. The double-orange granules comprise the following raw materials: a volatile oil inclusion compound, dry paste powder, low-viscosity dextrin, powdered sugar and amber powder. The volatile oil clathrate compound is prepared by the following steps: adding water into beta-cyclodextrin, uniformly mixing, and then adding volatile oil for clathration, thereby obtaining the volatile oil clathrate compound. The mass ratio of the beta-cyclodextrin to the water is 1: (4-6), the mass ratio of the volatile oil to the beta-cyclodextrin is 1: (9-12), and the dry paste powder is prepared by adding the double-orange particle extract into low-viscosity dextrin and carrying out spray drying. The preparation method of the double-orange granules comprises the following steps: mixing all the raw materials, granulating by taking a 55-65% ethanol water solution as an adhesive, finishing the granules, drying, and finishing the granules again. According to the invention, by optimizing the variety and dosage of the auxiliary materials, the tower sticking phenomenon in spray drying can be obviously improved, and the yield of spray drying and the particle yield of wet granulation are improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to Shuangju granules and a preparation method thereof. Background Art

[0002] Shuangju Granules (Approval Number: National Medicine Standard Z20070021), an exclusive product of Jiangxi Nanchang Jisheng Pharmaceutical Co., Ltd., are composed of jinggucao, baiying, guazijin, amber, huajuhong, coix seed, and tangerine seed. They are known to clear the liver and regulate qi, promote blood circulation and remove blood stasis. They are used for uterine fibroids characterized by a combination of qi stagnation, blood stasis, and phlegm-heat syndrome according to Traditional Chinese Medicine. Symptoms include heavy or prolonged menstruation, breast tenderness, lower abdominal distension or dull pain, a feeling of anal heaviness, profuse or yellowish vaginal discharge, a red or dark red tongue with ecchymosis or petechiae, a greasy or yellowish tongue coating, and a deep, stringy, or fine, or slippery or wiry pulse.

[0003] The raw materials for Shuangju granules include 1000g of Atractylodes macrocephala, 1000g of Bletilla striata, 500g of Ginger Seeds, 100g of Amber, 333.3g of Citrus aurantium, 666.7g of Coix seeds, and 500g of Citrus aurantium seeds. The volatile oil extracted from Citrus aurantium is volatile, and the inclusion rate of the volatile oil inclusion compound obtained using existing inclusion technology is low. Furthermore, when the extract concentrate is spray-dried, the material exhibits significant sticking during the drying process, resulting in unstable spray-drying yields. Furthermore, the granule yield during wet granulation is low, and the soft material exhibits lumps. Summary of the Invention

[0004] In order to overcome the above technical problems, the present invention provides a double orange granule and a preparation method thereof.

[0005] To achieve the above objectives, the technical solutions provided by the present invention are as follows: The invention discloses double orange granules, wherein the raw materials of the double orange granules include the following components: volatile oil inclusion compound, dry paste powder, low-viscosity dextrin, powdered sugar and amber powder.

[0006] The preparation of the volatile oil inclusion compound comprises mixing beta-cyclodextrin with water, and then adding volatile oil for inclusion; the mass ratio of beta-cyclodextrin to water is 1:4-6, and the mass ratio of volatile oil to beta-cyclodextrin is 1:9-12.

[0007] The dry paste powder is prepared by adding double orange granule extract to low viscosity dextrin and performing spray drying.

[0008] Furthermore, the inclusion temperature is 45-55°C, the inclusion time is 40-50 minutes, and the product is dried at 40-50°C after inclusion.

[0009] Furthermore, in the preparation of the dry paste powder, the amount of low-viscosity dextrin added is 5-15wt% of the Shuangju granule extract powder.

[0010] Furthermore, the process parameters of the spray drying include an air inlet temperature of 160-180°C, an air outlet temperature of 80-100°C, and an atomizer speed of 16000-18000 r / min.

[0011] Furthermore, the Shuangju granule extract is an extract obtained by extracting Citrus aurantium, Atractylodes macrocephala, Bletilla striata, Glehnia littoralis, Citrus aurantium and Coix seed.

[0012] Furthermore, the preparation of the Shuangju granule extract includes first extracting coix seed with alcohol to obtain an alcohol extract and a medicinal residue 1, extracting volatile oil from tangerine peel to obtain a medicinal residue 2, then combining scutellaria baicalensis, white scutellaria baicalensis, golden peony root, tangerine seed, medicinal residue 1 and medicinal residue 2 to extract with water and precipitate with alcohol to obtain a water extract, and finally mixing the alcohol extract and the water extract and concentrating them to obtain the extract, or continuing to dry after concentration to obtain the extract.

[0013] Furthermore, the raw materials of the Shuangju granule extract include the following traditional Chinese medicines in parts by weight: 90-110 parts of Atractylodes macrocephala, 90-110 parts of Bletilla striata, 45-55 parts of Glehnia littoralis, 30-40 parts of Citrus aurantium, 60-70 parts of Coix seed and 45-55 parts of Citrus aurantium.

[0014] Furthermore, the raw materials of the Shuangju granules include the following components, by weight: 0.3-0.7 parts of a volatile oil inclusion compound, 15-25 parts of dry paste powder, 25-60 parts of low-viscosity dextrin, 20-30 parts of powdered sugar, and 5-15 parts of amber powder. Preferably, 0.3-0.7 parts of a volatile oil inclusion compound, 15-25 parts of dry paste powder, 40-45 parts of low-viscosity dextrin, 20-30 parts of powdered sugar, and 5-15 parts of amber powder are used.

[0015] Furthermore, the raw materials also include 0.5-1 parts of stevia as a flavoring agent, calculated by weight.

[0016] Another object of the present invention is to provide a method for preparing the double orange granules, comprising the following steps: (1) Mix the volatile oil inclusion compound, low-viscosity dextrin, powdered sugar, amber powder, and dry paste powder, or add flavoring agents, and then granulate with 55-65% ethanol as a binder; (2) The granules are granulated, dried, and granulated again.

[0017] Preferably, the granules obtained in step (2) are sieved through a 14-18 mesh sieve, dried at 55-65° C. for 50-70 min, and granulated again after the material is dried.

[0018] Compared with the prior art, the technical advantages of the present invention are: 1. The present invention adds a specific proportion of low-viscosity dextrin to the extract, which can significantly improve the sticking tower phenomenon during spray drying and increase the yield of spray drying compared with other auxiliary materials such as dextrin, maltodextrin DE10, maltodextrin DE15, maltodextrin DE18 and starch.

[0019] 2. The present invention further investigated the effects of different drying methods on the yield and found that spray drying had a better yield.

[0020] 3. Volatile oil sprayed directly into the particles is easy to volatilize, affecting the stability and efficacy of the preparation; and will lead to a bad taste. The inclusion of volatile oil through a specific process can well cover up the bad smell of volatile oil and improve the stability of the preparation.

[0021] 4. The present invention explored the wet granulation process and found that when low-viscosity dextrin was used for wet granulation, the soft material was in good condition and the granule yield was about 90%, which was significantly better than the granule yield using other excipients or without excipients. DETAILED DESCRIPTION

[0022] The present invention is described below through specific examples to facilitate understanding and grasp of the technical solutions of the present invention, but the present invention is not limited thereto. The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified. The ethanol concentrations mentioned herein are all volume concentrations. The commercial information of the auxiliary materials is as follows: Low-viscosity dextrin (202408005, Langfang Shengtai Pharmaceutical Co., Ltd.); Dextrin (2502009, Shandong Liaocheng Ahua Pharmaceutical Co., Ltd.); Starch (20220310, Qufu Tianli Pharmaceutical Excipients Co., Ltd.); DE10 maltodextrin (TF70211205, Hunan Jiudian Hongyang Pharmaceutical Co., Ltd.); DE15 maltodextrin (TF70240502, Hunan Jiudian Hongyang Pharmaceutical Co., Ltd.); DE18 maltodextrin (20220101, Baolingbao Biotechnology Co., Ltd.); Powdered sugar (2410013, COFCO Chongzuo Sugar Co., Ltd.).

[0023] Example 1 1000g of Atractylodes macrocephala, 1000g of Sophora flavescens, 500g of Melon Seed Gold, 100g of Amber, 333.3g of Tangerine Peel, 666.7g of Coix Seed, 500g of Tangerine Seed The preparation methods of the volatile oil inclusion compound, Shuangju granule extract, and dry paste powder are as follows: (1) Crush the above seven ingredients and pass the amber through a 100-mesh sieve, and set aside.

[0024] (2) Extract volatile oil from tangerine peel by steam distillation, collect the oil, and set aside the residue 1; add beta-cyclodextrin to water and stir, slowly add volatile oil dropwise, wherein the mass ratio of volatile oil to beta-cyclodextrin is 1:10; the mass ratio of beta-cyclodextrin to water is 1:6, stir at a constant temperature of 50°C for 45 minutes, and refrigerate at a constant temperature of 4°C for 18 hours. Filter the resulting inclusion complex solution and dry it in an oven at 50°C to obtain the volatile oil inclusion complex; (3) Coix seed was extracted twice with 60% ethanol by reflux, each time for 2 hours, filtered, and the filtrate and the residue 2 were obtained. The residue and other medicinal materials were decocted with water twice, each time for 2 hours. The two decoctions were combined, filtered, and concentrated under reduced pressure to a clear paste with a relative density of 1.15-1.20 (80°C). Ethanol was added to make the alcohol content reach 60%. The mixture was allowed to stand for 24 hours. The supernatant was taken and combined with the coix seed alcohol extract. The ethanol was recovered and concentrated to a Shuangju granule extract with a relative density of 1.15-1.20 (80°C). Low-viscosity dextrin of 10% by mass of the Shuangju granule extract was added and spray-dried (inlet air temperature 170°C, outlet air temperature 90°C, atomizer speed 18000 r / min) to obtain a dry paste powder.

[0025] The raw materials of Shuangju granules are as follows: Calculated by weight, the ingredients include 0.5 parts of volatile oil inclusion compound, 18.2 parts of dry paste powder, 10 parts of amber powder, 44.5 parts of low-viscosity dextrin, 26 parts of powdered sugar and 0.8 parts of stevia as a flavoring agent.

[0026] The preparation method is as follows: (1) Mix the volatile oil inclusion compound, low-viscosity dextrin, powdered sugar, amber powder, stevia and dry paste powder, and perform wet granulation using 55% ethanol aqueous solution as a binder; (2) The obtained granules are sized using an 18-mesh sieve granulator, dried at 65°C for 50 min, and sized again after the material is dry and passed through an 18-mesh sieve.

[0027] Example 2 1000g of Atractylodes macrocephala, 1000g of Sophora flavescens, 500g of Melon Seed Gold, 100g of Amber, 333.3g of Tangerine Peel, 666.7g of Coix Seed, 500g of Tangerine Seed The preparation methods of the volatile oil inclusion compound, Shuangju granule extract, and dry paste powder are as follows: (1) Crush the above seven ingredients and pass the amber through a 100-mesh sieve, and set aside.

[0028] (2) Extract volatile oil from dried tangerine peel by steam distillation, collect the oil, and set aside the residue 1; add beta-cyclodextrin to water and stir, slowly add volatile oil dropwise, stir at a constant temperature of 45°C for 50 minutes, and refrigerate at a constant temperature of 4°C for 18 hours. Filter the resulting inclusion complex solution and dry it in an oven at 45°C to obtain the volatile oil inclusion complex; the mass ratio of volatile oil to beta-cyclodextrin is 1:12; the mass ratio of beta-cyclodextrin to water is 1:4.

[0029] (3) Coix seed was extracted twice with 60% ethanol under reflux, each time for 2 hours, filtered, and the filtrate and the residue 2 were obtained. The residue and other medicinal materials were decocted with water twice, each time for 2 hours. The two decoctions were combined, filtered, and concentrated under reduced pressure to a clear paste with a relative density of 1.15-1.20 (80°C). Ethanol was added to make the alcohol content reach 60%. The mixture was allowed to stand for 24 hours. The supernatant was taken and combined with the coix seed alcohol extract. The ethanol was recovered and concentrated to a Shuangju granule extract with a relative density of 1.15-1.20 (80°C). Low-viscosity dextrin was added at 5% of the mass of Shuangju granule extract, and the mixture was spray-dried (inlet air temperature 180°C, outlet air temperature 100°C, atomizer speed 16000r / min) to obtain a dry paste powder.

[0030] The raw materials of Shuangju granules are as follows: (1) 0.3 parts of volatile oil inclusion compound, 15 parts of dry paste powder, 5 parts of amber powder, 58.9 parts of low-viscosity dextrin, 20 parts of powdered sugar and 0.8 parts of stevia flavoring agent.

[0031] The preparation method is as follows: (1) Mixing the volatile oil inclusion compound, low-viscosity dextrin, powdered sugar, amber powder, stevia and dry paste powder, and wet granulating the mixture using 65% ethanol aqueous solution as a binder; (2) The granules were sized using a 14-mesh granulator and dried at 55°C for 70 min. After the material was dry, it was sized again and passed through a 14-mesh sieve.

[0032] Example 3 1000g of Atractylodes macrocephala, 1000g of Sophora flavescens, 500g of Melon Seed Gold, 100g of Amber, 333.3g of Tangerine Peel, 666.7g of Coix Seed, 500g of Tangerine Seed The preparation methods of the volatile oil inclusion compound, Shuangju granule extract powder, and dry extract powder are as follows: (1) Crush the above seven ingredients and pass the amber through a 100-mesh sieve, and set aside.

[0033] (2) Extract volatile oil from dried tangerine peel by steam distillation, collect the oil, and set aside the residue 1; add beta-cyclodextrin with water and stir, slowly add volatile oil dropwise, stir at a constant temperature of 55°C for 40 minutes, and refrigerate at a constant temperature of 4°C for 18 hours. Filter the resulting inclusion complex solution and dry it in an oven at 40°C to obtain the volatile oil inclusion complex; the mass ratio of volatile oil to beta-cyclodextrin is 1:9; the mass ratio of beta-cyclodextrin to water is 1:5.

[0034] (3) Coix seed was extracted twice with 60% ethanol by reflux, each time for 2 hours, filtered, and the filtrate and the residue 2 were obtained. The residue and other medicinal materials were decocted with water twice, each time for 2 hours. The two decoctions were combined, filtered, and concentrated under reduced pressure to a clear paste with a relative density of 1.15-1.20 (80°C). Ethanol was added to make the alcohol content reach 60%. The mixture was allowed to stand for 24 hours. The supernatant was taken and combined with the alcohol extract of coix seed. The ethanol was recovered and concentrated to a Shuangju granule extract with a relative density of 1.15-1.20 (80°C). Low-viscosity dextrin of 15% by mass of Shuangju granule extract was added and spray-dried (inlet air temperature 160°C, outlet air temperature 80°C, atomizer speed 17000r / min) to obtain a dry paste powder.

[0035] The raw materials of Shuangju granules are as follows: 0.7 parts of volatile oil inclusion compound, 25 parts of dry paste powder, 15 parts of amber powder, 30 parts of powdered sugar, 28.5 parts of low-viscosity dextrin and 0.8 parts of flavoring agent stevia.

[0036] The preparation method is as follows: (1) Mixing the volatile oil inclusion compound, low-viscosity dextrin, powdered sugar, amber powder, stevia and dry paste powder, and wet granulating the mixture using 60% ethanol aqueous solution as a binder; (2) The obtained granules were sized using a 14-mesh sieve granulator, dried at 60°C for 60 min, and sized again after the material was dried and passed through a 14-mesh sieve.

[0037] Comparative Example 1 The only difference between this comparative example and Example 1 is that the mass ratio of beta-cyclodextrin to volatile oil is 8:1.

[0038] Comparative Example 2 The only difference between this comparative example and Example 1 is that the mass ratio of beta-cyclodextrin to water is 1:8.

[0039] Comparative Example 3 The only difference between this comparative example and Example 1 is that the inclusion temperature is different, specifically 40°C.

[0040] Comparative Example 4 The only difference between this comparative example and Example 1 is that the inclusion temperature is different, specifically 60°C.

[0041] Comparative Example 5 The only difference between this comparative example and Example 1 is that the inclusion time is different, specifically 60 minutes.

[0042] Comparative Example 6 The only difference between this comparative example and Example 1 is that the inclusion time is different, specifically 30 minutes.

[0043] Comparative Example 7 The only difference between this comparative example and Example 1 is that the drying temperature after inclusion is 60°C.

[0044] Comparative Example 8 The only difference between this comparative example and Example 1 is that low-viscosity dextrin is not added to the raw materials of the double orange granules, but an equal amount of dextrin is added.

[0045] Comparative Example 9 The only difference between this comparative example and Example 1 is that low-viscosity dextrin is not added to the raw materials of the double orange granules, but an equal amount of starch is added.

[0046] Comparative Example 10 The only difference between this comparative example and Example 1 is that low-viscosity dextrin is not added to the raw materials of the double orange granules, but an equal amount of maltodextrin DE10 is added.

[0047] Comparative Example 11 The only difference between this comparative example and Example 1 is that in the preparation of the dry paste powder, no low-viscosity dextrin is added during spray drying.

[0048] Comparative Example 12 The only difference between this comparative example and Example 1 is that in the preparation of the dry paste powder, the low-viscosity dextrin is replaced by dextrin during spray drying.

[0049] Comparative Example 13 The only difference between this comparative example and Example 1 is that in the preparation of the dry paste powder, the low-viscosity dextrin is replaced by starch during spray drying.

[0050] Comparative Example 14 The only difference between this comparative example and Example 1 is that the drying method of spray drying is changed to belt vacuum drying, and the process parameters are: heating zone temperatures of 100°C, 110°C, 90°C, and 35°C, a conveying speed of 20 Hz, and a vacuum degree of -100 KPa.

[0051] Comparative Example 15 The only difference between this comparative example and Example 1 is that, in the preparation of the dry paste powder, the low-viscosity dextrin used in the spray drying is replaced with maltodextrin DE10.

[0052] Comparative Example 16 The only difference between this comparative example and Example 1 is that, in the preparation of the dry paste powder, the low-viscosity dextrin used in the spray drying is replaced with maltodextrin DE15.

[0053] Comparative Example 17 The only difference between this comparative example and Example 1 is that, in the preparation of the dry paste powder, the low-viscosity dextrin used in the spray drying is replaced with maltodextrin DE18.

[0054] Experiment 1 The volatile oil in the volatile oil inclusion complexes of Examples 1-3 and Comparative Examples 1-7 was determined by adding 30 g of the dried inclusion complex and 600 ml of pure water into a 1 L round-bottom flask, connecting a volatile oil extractor, and determining the volatile oil content according to Method A of Volatile Oil Determination in Chinese Pharmacopoeia 2204.

[0055] Inclusion compound yield (%) = inclusion compound amount g / (cyclodextrin amount + volatile oil amount) g × 100%.

[0056] Inclusion rate (%) = volume of volatile oil in inclusion complex ml / (volume of volatile oil added × blank recovery rate) ml × 100%, blank recovery rate = 87.3%.

[0057] Comprehensive scoring calculation method: The total score is 100 points, the inclusion compound yield accounts for 20 points, and the volatile oil inclusion rate accounts for 80 points. The results are shown in Table 1.

[0058] Table 1

[0059] Experiment 2 The spray drying processes of Examples 1-3 and Comparative Examples 11-17 were studied, and the results are shown in Table 2 below: Table 2

[0060] Experiment 3: Granulation process investigation The granulation processes of Example 1 of the present invention and Comparative Examples 8-10 were investigated respectively, and the results are shown in Table 3.

[0061] Table 3

[0062] Experiment 4: Stability Experiment The packaged Shuangju granules were placed in a stability test chamber and subjected to a one-year accelerated stability test. The stability results met the standards for granules, demonstrating that the low-viscosity dextrin of the present invention was superior to granules prepared with other excipients.

[0063] The above detailed description is a specific description of one feasible embodiment of the present invention. This embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or modification that does not depart from the present invention should be included in the scope of the technical solution of the present invention.

Claims

1. A double orange granule, characterized in that: The raw materials of the double orange granules include volatile oil inclusion compound, dry paste powder, low viscosity dextrin, powdered sugar and amber powder; The preparation of the volatile oil inclusion compound comprises mixing beta-cyclodextrin with water, and then adding volatile oil for inclusion; the mass ratio of beta-cyclodextrin to water is 1:4-6, and the mass ratio of volatile oil to beta-cyclodextrin is 1:9-12; The preparation of the dry paste powder comprises the steps of adding the double orange granule extract to low-viscosity dextrin and performing spray drying.

2. The double orange granules according to claim 1, characterized in that The inclusion temperature is 45-55° C., the inclusion time is 40-50 min, and after inclusion, the product is dried at 40-50° C.

3. The double orange granules according to claim 1, characterized in that In the preparation of the dry paste powder, the amount of low-viscosity dextrin added is 5-15wt% of the Shuangju granule extract.

4. The double orange granules according to claim 1, characterized in that The process parameters of the spray drying include an air inlet temperature of 160-180°C, an air outlet temperature of 80-100°C, and an atomizer speed of 16000-18000 r / min.

5. The double orange granules according to claim 1, characterized in that The preparation of the Shuangju granule extract comprises the following steps: firstly extracting coix seed with alcohol to obtain an alcohol extract and a medicinal residue 1, extracting volatile oil from tangerine peel to obtain a medicinal residue 2, then combining scutellaria baicalensis, white scutellaria baicalensis, golden osmanthus fragrans, tangerine seed, medicinal residue 1 and medicinal residue 2, extracting with water and precipitating with alcohol to obtain a water extract, and finally mixing the alcohol extract and the water extract to concentrate to obtain an extract with a relative density of 1.15 to 1.20 at 80° C., or continuing to dry after concentration to obtain the extract.

6. The double orange granules according to any one of claims 1 to 5, characterized in that: The raw materials of the Shuangju granule extract include the following Chinese medicinal materials in parts by weight: 90-110 parts of Atractylodes macrocephala, 90-110 parts of Bletilla striata, 45-55 parts of Glehnia littoralis, 30-40 parts of Citrus aurantium, 60-70 parts of Coix seeds and 45-55 parts of Citrus aurantium.

7. The double orange granules according to any one of claims 1 to 5, characterized in that The raw materials of the double orange granules include the following components in parts by weight: 0.3-0.7 parts of volatile oil inclusion compound, 15-25 parts of dry paste powder, 25-60 parts of low-viscosity dextrin, 20-30 parts of powdered sugar and 5-15 parts of amber powder.

8. The double orange granules according to claim 7, characterized in that The raw materials also include 0.5-1 parts of flavoring agents by weight.

9. A method for preparing the double orange granules according to any one of claims 1 to 8, characterized in that: The steps include: (1) Mix the volatile oil inclusion compound, low-viscosity dextrin, powdered sugar, amber powder, and dry paste powder, or add flavoring agents, and then granulate with 55-65% ethanol as a binder; (2) The granules are granulated, dried, and granulated again.

10. The preparation method according to claim 9, characterized in that The granulation in step (2) is to pass through a 14-18 mesh sieve, dry the granules at 55-65°C for 50-70 minutes, and then granulate the granules again after the material is dried.

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