A preparation method of Lingguishugan decoction granules

Abstract

The present invention provides a preparation method of Ling Gui Shu Gan Tang granules, and relates to the technical field of traditional Chinese medicine compound granules. The present invention discloses a preparation method of Ling Gui Shu Gan Tang granules, comprising the following steps: 1) extraction: extracting the raw materials with water to obtain an extract; the raw materials are composed of Poria cocos, cinnamon twig, Atractylodes macrocephala and liquorice; 2) concentration: separating the extract and then vacuum concentrating to obtain a concentrate; 3) drying: spray drying the concentrate to obtain an extract powder; 4) mixing: mixing the extract powder and auxiliary materials to obtain a mixture; the auxiliary materials are selected from maltodextrin and magnesium stearate or soluble starch and magnesium stearate; 5) granulation: dry granulating the mixture. The present invention provides a preparation method with uniform particles and easy granulation by investigating the types of auxiliary materials and granulation process parameters, which is convenient for wide promotion.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine compound granules, and in particular to a preparation method of Lingguishugan decoction granules. Background Art

[0002] The recipe of Ling Gui Zhu Gan Tang comes from Zhang Zhongjing's Treatise on Febrile and Miscellaneous Diseases. Article 67 of the book says: "For patients with febrile diseases, if after vomiting or purgation, the heart is full and the qi rushes up to the chest, the head is raised when standing up, the pulse is deep and tight, and the menstruation is disturbed when sweating, and the body is shaking, Fuling Guizhi Baizhu Gancao Tang is the main treatment." This recipe is also included in the Synopsis of the Golden Chamber, which says: "If there is phlegm and fluid under the heart, fullness in the chest and ribs, and dizziness, Ling Gui Zhu Gan Tang is the main treatment." Ling Gui Zhu Gan Tang is a dampness-removing agent with the effects of warming yang, transforming fluid, strengthening the spleen and removing dampness. It is mainly used to treat phlegm and fluid caused by insufficient middle yang. Fullness in the chest and ribs, dizziness, palpitations, shortness of breath and cough, white and slippery tongue coating, and stringy and slippery or deep and tight pulse. It is often used in the clinic to treat chronic bronchitis, bronchial asthma, cardiogenic edema, chronic glomerulonephritis edema, Meniere's disease, neurosis, etc., which are caused by water retention in the middle jiao.

[0003] The existing Ling Gui Shu Gan Tang is mainly a decoction, which is inconvenient to use. Decoction is the most commonly used traditional dosage form in Chinese clinical medicine, which is convenient for syndrome differentiation and treatment, addition and subtraction, but it has a poor taste, is inconvenient to carry, and is difficult for patients to accept. Granules are closest to traditional decoctions in terms of taking methods, and are convenient to carry and take. They are one of the important dosage forms of current Chinese medicine compound preparations. Chinese medicine granules are a new dosage form developed on the basis of dosage forms such as Chinese medicine decoctions and dry syrups. They not only retain the characteristics of fast absorption and rapid action of decoctions, but also overcome the shortcomings of inconvenience in decoction, large dosage, poor taste, easy mildew and deterioration, as well as the shortcomings of poor absorption and slow effect of pills and tablets. It is a suitable preparation for the treatment of cardiovascular diseases. In addition, the preparation process of granules is suitable for industrial production, the product quality is stable, and it is convenient to take, carry, store and transport.

[0004] Granules are currently mainly divided into two types: wet granulation and dry granulation. Dry granulation technology can be completed by a drum flat-pressing granulator. The Chinese medicine extract with a certain relative density is spray-dried to obtain a dry extract powder. After adding certain excipients, it is pressed into thin sheets by a dry extrusion granulator and then crushed into granules. This method requires fewer excipients, which is beneficial to improving the stability, disintegration and solubility of the granules. However, it should also be noted that the dry extract obtained by spray drying has strong hygroscopicity. Therefore, the key to the application of this method is to find suitable excipients. The excipients must have a certain degree of adhesion and are not easy to absorb moisture, such as lactose, pregelatinized starch, mannitol, water-soluble acrylic resins and cellulose derivatives. The second key point of applying this method is to control the granulation process.

[0005] Existing patents disclose the preparation of Ling Gui Shu Gan Tang granules by dry granulation, but do not disclose the effects of relevant spray drying parameters and granulation parameters on the granules. In view of this, the present invention discloses a preparation method with uniform granules that are easy to granulate by exploring the effects of excipient types and granulation process parameters on the preparation of Ling Gui Shu Gan Tang granules. Summary of the invention

[0006] The purpose of the present invention is to provide a preparation method of Ling Gui Shu Gan Tang granules, and to obtain Ling Gui Shu Gan Tang granules with stable and controllable quality by screening the types of auxiliary materials for dry granulation and the optimal parameters in the granulation process.

[0007] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0008] The present invention provides a method for preparing Lingguishugan decoction granules, comprising the following steps:

[0009] 1) Extraction: extracting the raw materials with water to obtain an extract; the raw materials are composed of Poria cocos, cinnamon twig, Atractylodes macrocephala and liquorice;

[0010] 2) Concentration: Separate the extract and then concentrate it in vacuum to obtain a concentrate;

[0011] 3) Drying: spray drying the concentrated solution to obtain extract powder;

[0012] 4) Mixing: Mixing the extract powder, auxiliary materials and magnesium stearate to obtain a mixture; the auxiliary materials are selected from maltodextrin and magnesium stearate or soluble starch and magnesium stearate; the amount of maltodextrin or soluble starch is 45%-55% of the weight of the extract powder, and the amount of magnesium stearate is 0.7-0.8% of the weight of the extract powder;

[0013] 5) Granulation: The mixed material is subjected to dry granulation. The parameters of dry granulation include: roller pressure of 20-30 bar, feed speed of 16-25 rpm and roller speed of 2-5 rpm.

[0014] Preferably, the raw materials in step 1) are 4 parts of Poria cocos, 3 parts of cinnamon twig, 3 parts of Atractylodes macrocephala, and 2 parts of liquorice.

[0015] Preferably, the specific parameters of the extraction in step 1) include: extraction temperature of 95-98°C, extraction 1-3 times and extraction time of 120-140min; further preferably, the specific parameters of the extraction include: extraction temperature of 95°C, extraction 1 time and extraction time of 135min.

[0016] Preferably, the extraction endpoint of the extraction in step 1) is: the online detection of the concentration of liquiritin in the extract is 90-110 μg / g, the concentration of glycyrrhizic acid is 210-230 μg / g, the concentration of cinnamic acid is 10-20 μg / g and the solid content is 2-3%; further preferably, the extraction endpoint of the extraction is: the online detection of the concentration of liquiritin in the extract is 100 μg / g, the concentration of glycyrrhizic acid is 220 μg / g, the concentration of cinnamic acid is 15 μg / g and the solid content is 2.5%.

[0017] Preferably, the separation in step 2) is selected from at least one of centrifugation, filtration, liquid separation, distillation and fractionation; most preferably, the separation is centrifugation.

[0018] Preferably, the specific parameters of the centrifugation are a frequency of 40-60 Hz and a pressure of 0.1-0.2 MPa; further preferably, the specific parameters of the centrifugation are a frequency of 50 Hz and a pressure of 0.15 MPa.

[0019] Preferably, the specific parameters of the vacuum concentration in step 3) include a vacuum degree of -0.085 to -0.01 MPa and a temperature of 35-65°C; further preferably, the specific parameters of the vacuum concentration include a vacuum degree of -0.9 MPa and a temperature of 45°C.

[0020] Preferably, the relative density of the concentrated solution in step 3) is 1.10-1.15; most preferably, it is 1.10.

[0021] Preferably, the specific parameters of the spray drying in step 3) are: inlet air temperature of 140-160°C, feed rate of 15-20rmp, outlet air temperature of 70-90°C and atomizer speed of 13000-14000rpm; further preferably, the specific parameters of the spray drying in step 3) are: inlet air temperature of 140°C, 160°C, feed rate of 15rmp, 20rmp, outlet air temperature of 75-85°C and atomizer speed of 13200-13800rpm; most preferably, the inlet air temperature is 140°C, the feed rate is 15rmp, the outlet air temperature is 82°C and the atomizer speed is 13500rpm.

[0022] Preferably, the auxiliary materials in step 4) are maltodextrin and magnesium stearate.

[0023] Preferably, the amount of the auxiliary material in step 4) is 53% by weight of the extract powder.

[0024] Preferably, the amount of magnesium stearate used in step 4) is 0.77% by weight of the extract powder.

[0025] Preferably, the specific parameters of the mixing in step 4) are: a rotation speed of 10-20 r / min, and a total mixing time of 10-50 min; more preferably, the rotation speed is 18 r / min, and the total mixing time is 40 min.

[0026] Preferably, the parameters of the dry granulation in step 5) include: a roller pressure of 23-28 bar, a feed speed of 18-20 rpm and a roller speed of 2.5-3.5 rpm; most preferably, the parameters of the dry granulation include: a roller pressure of 23 bar, a feed speed of 18.7 rpm and a roller speed of 2.8 rpm.

[0027] Step 5) The mesh size of the sieve is 10-24 meshes.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The invention provides a preparation method with uniform particles and easy granulation by examining the types of auxiliary materials and granulation process parameters, which is convenient for wide promotion. DETAILED DESCRIPTION

[0030] In order to make the technical means, creative features, purpose and effect of the present invention easy to understand, the present invention is further explained below in conjunction with specific embodiments, but the following embodiments are only preferred embodiments of the present invention, not all. Based on the embodiments in the implementation mode, other embodiments obtained by those skilled in the art without making creative work all belong to the protection scope of the present invention. It is worth noting that the raw materials used in the present invention are all common commercial products, and their sources are not specifically limited. The technology and scientific terms used in the embodiments have the meanings commonly understood by those of ordinary skill in the art to which the present invention belongs.

[0031] Example 1

[0032] 1) Extraction: Weigh the raw materials according to the proportion, 4 parts of Poria cocos, 3 parts of cinnamon twig, 3 parts of Atractylodes macrocephala, and 2 parts of liquorice, place them in an extraction hanging basket, add 10 times the amount of purified water for cyclic dynamic extraction, the extraction temperature is 95°C, the extraction is performed once, the extraction time is 135 minutes, and the extract is obtained. The extraction endpoint is determined by online detection technology during the decoction process;

[0033] The endpoint indicators of the online detection extraction are: the concentration of liquiritin in the online detection extract is 100 μg / g, the concentration of glycyrrhizic acid is 220 μg / g, the concentration of cinnamic acid is 15 μg / g and the solid content is 2.5%.

[0034] 2) Concentration: The extract is separated by a centrifuge to obtain a centrifuge, the centrifuge frequency is 50 Hz, and the pressure is 0.15 MPa; the centrifuge enters the automatic continuous vacuum concentration module through a pipeline for plate concentration, and the vacuum degree during concentration is -0.9 MPa and the temperature is 45°C.

[0035] 3) Drying: The concentrate was input into a spray dryer for drying. The relative density of the concentrate was 1.10, the inlet air temperature was 140° C., the feed rate was 15 rpm, the outlet air temperature was 82° C., and the atomizer speed was 13500 rpm to obtain Ling Gui Zhu Gan Tang extract powder.

[0036] 4) Mixing: The extract powder, maltodextrin and magnesium stearate are placed in a hopper mixer for total mixing, wherein the amount of maltodextrin is 53% of the weight of the extract powder, the amount of magnesium stearate is 0.77% of the weight of the extract powder, the mixer speed is 18 r / min, and the total mixing time is 40 min.

[0037] 5) Granulation: The mixed material was placed in a dry granulator for dry granulation. The dry granulation parameters were as follows: roller pressure 23 bar, feed speed 18.7 rpm, roller speed 2.8 rpm, and the whole granules were passed through a 20-mesh sieve.

[0038] Example 2

[0039] The preparation method is the same as that in Example 1, except that the relative density of the concentrate in step 3) is changed to 1.12, the inlet air temperature is changed to 160°C, and the feed speed is 20 rpm; the roller pressure in step 5) is changed to 28 bar, the feed speed is changed to 18 rpm, and the roller speed is changed to 2.5 rpm.

[0040] Example 3

[0041] The preparation method is the same as that in Example 1, except that the relative density of the concentrate in step 3) is changed to 1.15, the inlet air temperature is changed to 150°C, and the feed speed is 18 rpm; the maltodextrin in step 4) is changed to magnesium stearate; the roller pressure in step 5) is changed to 25 bar, the feed speed is changed to 20 rpm, and the roller speed is changed to 3 rpm.

[0042] Comparative Example 1

[0043] The preparation method is the same as that in Example 1, except that the air inlet temperature of the concentrated solution in step 3) is changed to 180°C.

[0044] Comparative Example 2

[0045] The preparation method is the same as that of Example 1, except that the feed rate in step 3) is changed to 10 rpm.

[0046] Comparative Example 3

[0047] The preparation method is the same as that in Example 1, except that the relative density of the concentrated solution in step 3) is changed to 1.21.

[0048] Comparative Example 4

[0049] The preparation method is the same as that of Example 1, except that the maltodextrin in step 4) is replaced by powdered sugar.

[0050] Comparative Example 5

[0051] The preparation method is the same as that of Example 1, except that the maltodextrin in step 4) is replaced by lactose.

[0052] Comparative Example 6

[0053] The preparation method is the same as that in Example 1, except that the feeding speed in step 5) is changed to 23.7 rpm.

[0054] Comparative Example 7

[0055] The preparation method is the same as that of Example 1, except that the roller speed in step 5) is changed to 3.8 rpm.

[0056] Comparative Example 8

[0057] The preparation method is the same as that of Example 1, except that the weight ratio of maltodextrin to the extract powder in step 4) is changed to 20%, and the weight ratio of magnesium stearate to the extract powder is changed to 0.3%.

[0058] According to Examples 1-3 and Comparative Examples 1-3, the effects of the process parameters of spray drying during the granulation process on the granulation results were investigated, as shown in Table 1 and Table 2.

[0059] Table 1. Results of spray drying process parameters investigation

[0060]

[0061] It can be seen from the above data that, judging from the appearance, moisture, and powder yield, the process parameters of spray drying have a certain influence on the powder yield of the extract powder. The higher the inlet air temperature, the lower the powder yield of the extract powder, and the coarser and more uneven the extract powder is; when the feed rate is lower than 15rpm, the powder yield of the extract powder is not good; the greater the relative density of the feed liquid, the lower the powder yield of the extract powder. Therefore, the preparation method of the Ling Gui Shu Gan Tang granules in the embodiment of the present invention can effectively improve the quality of the extract powder. Among them, the optimal process parameters for spray drying of the concentrated solution of the Ling Gui Shu Gan Tang preparation are: inlet air temperature of 140°C, feed rate of 15rpm, and relative density of the feed liquid of 1.10 (60°C).

[0062] According to Examples 1-3 and Comparative Examples 4, 5, and 8, the effects of the types and proportions of auxiliary materials on the granulation results during the granulation process were investigated, as shown in Table 3.

[0063] Table 2. Results of investigation on auxiliary materials

[0064]

[0065]

[0066] It can be obtained from the above data that the auxiliary materials have a significant effect on the dry granulation of Lingguishugan Decoction. Powdered sugar and dextrin produce sticky wheels and black flakes during the dry granulation pressing process, and continuous granulation cannot be achieved; there are some black flakes in the soluble starch, resulting in poor solubility than maltodextrin, and the color of the particles is uneven; in addition, maltodextrin has good compressibility, and the material is easier to shape during the dry granulation process and is not easy to loose. At the same time, it was found that the mixed powder had poor fluidity during the granulation process, so that the feeding was not smooth enough, so magnesium stearate was added as a lubricant, and maltodextrin was compounded with magnesium stearate to effectively improve the quality of the granulation process. It can be seen from Comparative Example 8 that the ratio of maltodextrin to magnesium stearate in this embodiment is not easy to cause defects such as sticky wheels during the granulation process.

[0067] The influence of the process parameters on the granulation results during the granulation process was investigated according to Examples 1-3 and Comparative Examples 6-7, as shown in Table 3.

[0068] Table 3. Granulation parameter investigation results

[0069] sample Particle yield / % granularity / % Angle of repose Solubility / min Difficulty of granulation Example 1 74.2 7.8 33.02 0.5 Easy (no abnormality) Example 2 72.4 7.3 34.15 0.4 Easy (no abnormality) Example 3 74.1 6.8 33.31 0.4 Easy (no abnormality) Comparative Example 6 28.5 25.6 34.99 Presence of insoluble matter Difficult (slightly sticky wheel) Comparative Example 7 32.4 48.0 34.02 5.0 Difficult (black film)

[0070] From the above data, it can be seen that the process parameters in the dry granulation process have a significant impact on the granulation results. The process parameters have little effect on the angle of repose, and the granule fluidity is good. However, the greater the roller pressure, feed speed, and roller speed, the easier it is to stick to the wheel, and the more uneven the color and particle size of the prepared granules are, and there are difficult-to-dissolve black crumbs, and the solubility is poor. The granulation effect in the embodiment of the present invention is better than the comparative example data, wherein the dry granulation parameters are roller pressure of 23 bar, feed speed of 18.7 rpm, and roller speed of 2.8 rpm for the best effect.

[0071] In summary, the technical scheme in the embodiments of the present invention screens out the inlet air temperature, feed rate, relative density of the feed liquid in a specific spray drying process; the type of auxiliary materials and the roller pressure, feed rate and roller speed in the dry granulation process, and optimizes a preparation method of Ling Gui Zhu Gan Tang granules with simple granulation and high granulation rate, achieving technical effects unexpected from other preparation process parameters, effectively improving the quality of the preparation process, and can be used for industrial promotion.

[0072] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing Lingguishugan decoction granules, characterized in that: The following steps are involved: 1) Extraction: The raw material is extracted with water to obtain an extract; The raw materials are composed of Poria cocos, cinnamon twig, Atractylodes macrocephala and liquorice; 2) Concentration: Separate the extract and then concentrate it in vacuum to obtain a concentrate; 3) Drying: spray drying the concentrated solution to obtain extract powder; the relative density of the concentrated solution is 1.10-1.15; the specific parameters of the spray drying are: inlet air temperature is 140-160°C, feed speed is 15-20rmp, outlet air temperature is 70-90°C and atomizer speed is 13000-14000rpm; 4) Mixing: Mixing the extract powder and auxiliary materials to obtain a mixture; the auxiliary materials are selected from maltodextrin and magnesium stearate; the amount of maltodextrin is 45%-55% of the weight of the extract powder, and the amount of magnesium stearate is 0.7-0.8% of the weight of the extract powder; 5) Granulation: The mixed material is subjected to dry granulation. The parameters of dry granulation include: roller pressure of 23-28 bar, feed speed of 18-20 rpm and roller speed of 2.5-3 rpm.

2. The method for preparing Ling Gui Zhu Gan Tang granules according to claim 1, characterized in that: Step 1) The raw materials are 4 parts of Poria cocos, 3 parts of cinnamon twigs, 3 parts of Atractylodes macrocephala, and 2 parts of liquorice.

3. The method for preparing Ling Gui Zhu Gan Tang granules according to claim 1, characterized in that: The specific parameters of the extraction in step 1) include: extraction temperature of 90-100° C., extraction times of 1-3 times, and extraction time of 120-140 min.

4. The method for preparing Lingguishugantang granules according to claim 1, characterized in that: The extraction endpoint of step 1) is: the concentration of liquiritin in the extract is 90-110 μg / g, the concentration of glycyrrhizic acid is 210-230 μg / g, the concentration of cinnamic acid is 10-20 μg / g and the solid content is 2-3%.

5. The method for preparing Lingguishugantang granules according to claim 4, characterized in that: The extraction end point of the extraction is: the concentration of liquiritin in the online detection extract is 100 μg / g, the concentration of glycyrrhizic acid is 220 μg / g, the concentration of cinnamic acid is 15 μg / g and the solid content is 2.5%.

6. The method for preparing Ling Gui Zhu Gan Tang granules according to claim 1, characterized in that: The specific parameters of the mixing in step 4) are: a rotation speed of 10-20 r / min and a total mixing time of 10-50 min.

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