A drug for treating coronary heart disease and its preparation method

Abstract

The present invention belongs to the technical field of pharmaceutical preparation, and provides a drug for treating coronary heart disease and a preparation method thereof. The powder raw materials used as medicine in the drug of the present invention include: American ginseng, pseudo-ginseng, schizandra chinensis, salvia miltiorrhiza, chicken gizzard-membrane, dendrobium officinale, cordyceps sinensis, crocus sativus and hippocampus; the particle size range of the powder raw materials is: D90 is 125-145 μm, D50 is 50-100 μm, and D10 is 18-35 μm. By controlling the particle size and its distribution of the raw material powder, the present invention effectively improves the mixing uniformity of the effective active ingredients of the drug, and at the same time improves the powder fluidity, provides a basis for the quality uniformity of the subsequent finished product of Yi'anning Pills, and provides a guarantee for the stability of the clinical efficacy.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparation, and relates to a drug for treating coronary heart disease and its preparation method. Background Art

[0002] Yi An Ning Pills is a traditional Chinese medicine preparation mainly composed of 14 traditional Chinese medicines including American ginseng, dendrobium officinale, cordyceps sinensis, turtle shell, pilose antler, schizandra chinensis, chicken gizzard-membrane, saffron, notoginseng, ganoderma lucidum, snake gallbladder, salvia miltiorrhiza, and hippocampus. It has the effects of replenishing qi and activating blood circulation, nourishing the liver and strengthening the kidney, and calming the mind. It is used to treat chest tightness and shortness of breath, fear of cold and cold limbs, and numbness of hands and feet caused by qi and blood weakness and liver and kidney deficiency. It also has a certain effect on insomnia, forgetfulness, fatigue, and weakness of the waist and knees; clinically applicable to the treatment of coronary heart disease such as myocardial ischemia, angina pectoris, and myocardial infarction.

[0003] The main effective active ingredients of this drug in the treatment of diseases include the common ingredient ginsenoside Rb1 of American ginseng and notoginseng, the unique ingredient notoginsenoside R1 of notoginseng, and the unique ingredient salvianolic acid B of salvia miltiorrhiza, etc.; in the preparation process of oral solid preparations such as pills, material mixing is a key process in the production process. The purpose of this process is to make the mixed materials fully and evenly mixed to ensure that each unit dose of the materials contains equal amounts of effective active ingredients, thereby ensuring the uniformity of the finished product content.

[0004] The mixing uniformity is a general index for evaluating whether the material mixing process meets the requirements. The "Technical Guidelines for the Study of Mixing Uniformity and In-process Dosage Unit Uniformity of Oral Solid Preparations of Chemical Drugs (Trial)" clearly stipulates the acceptance criteria for the mixing uniformity of oral solid preparation materials. It is stipulated that at least 10 sampling points should be selected. When the relative deviation RSD of the content of the detected components at each sampling point ≤ 5%, the mixing uniformity meets the regulations. If RSD > 5%, the mixing uniformity is unacceptable.

[0005] Chinese invention patent CN101850066B discloses a traditional Chinese medicine composition granule and its preparation method. The traditional Chinese medicine composition granule is suitable for preventing and regulating diseases of the human cardiovascular and cerebrovascular systems and sub-healthy states such as decreased immunity and easy fatigue. It includes the following weight components of broken-wall powders: 3-18 parts of American ginseng broken-wall powder, 1-24 parts of notoginseng broken-wall powder, 6-36 parts of dendrobium officinale broken-wall powder, and 9-45 parts of salvia miltiorrhiza broken-wall powder. The particle size of the broken-wall powder is D90 between 5-75 μm. Through the control of the particle size of the broken-wall powder, the cell tissues of traditional Chinese medicines are fully exposed, and the effective components of traditional Chinese medicines are not damaged too much during the preparation, so that the utilization rate of the effective components of each medicine in the formula is significantly improved; the traditional Chinese medicine composition granule also has significant advantages such as high drug efficacy, high quality uniformity, convenient carrying and taking, and safety and reliability. However, this technology does not clarify the relevant mechanism for high quality uniformity of the preparation.

[0006] For Yi'an Ning Pills, there are significant differences in the particle size distribution, content uniformity, and fluidity of the active ingredients in the raw material powder obtained by different preparation processes. Therefore, it is necessary to optimize its preparation process to improve the mixing uniformity of the medicinal flavors in the form of powder for use in medicine, and further provide better physical and chemical performance indicators such as fluidity for the preparation of subsequent oral preparations; at the same time, it is also expected to further improve the therapeutic effect of oral preparations, such as improving the dissolution performance of active ingredients. Summary of the Invention

[0007] In view of the problems existing in the prior art, the present invention provides a drug for treating coronary heart disease and its preparation method. By optimizing and improving the pulverization process of the medicinal flavors in the form of powder in Yi'an Ning Pills, a powder drug with a suitable particle size distribution range is obtained, thereby greatly improving the mixing uniformity of the active ingredients of the drug, and at the same time improving the fluidity of the powder, providing a basis for the quality uniformity of the subsequent finished Yi'an Ning Pills and ensuring the stability of its clinical efficacy.

[0008] One of the objectives of the present invention is:

[0009] To provide a drug for treating coronary heart disease, the drug includes a raw material powder in the form of powder for use in medicine, and the particle size range of the raw material powder is: D90 is 125 - 145 μm, D50 is 50 - 100 μm, and D10 is 18 - 35 μm.

[0010] Further, the raw material powder in the form of powder for use in medicine includes: American ginseng, notoginseng, schizandra chinensis, salvia miltiorrhiza, chicken gizzard-membrane, dendrobium officinale, cordyceps sinensis, saffron, and hippocampus.

[0011] Even further, the powder raw materials are in the following parts by weight: 26.4 - 75.9 parts of American ginseng, 16.5 - 62.7 parts of notoginseng, 1.65 - 16.5 parts of schizandra chinensis, 1.65 - 26.4 parts of salvia miltiorrhiza, 1.65 - 16.5 parts of chicken gizzard-membrane, 3.3 - 14.0 parts of dendrobium officinale, 1.65 - 14.9 parts of cordyceps sinensis, 0.82 - 7.42 parts of saffron, and 0.82 - 7.42 parts of hippocampus.

[0012] Preferably, the powder raw materials are in the following parts by weight: 50 parts of American ginseng, 40 parts of notoginseng, 10 parts of schizandra chinensis, 10 parts of salvia miltiorrhiza, 10 parts of chicken gizzard-membrane, 8 parts of dendrobium officinale, 8 parts of cordyceps sinensis, 4 parts of saffron, and 4 parts of hippocampus.

[0013] In some embodiments of the present invention, the powder raw materials are obtained by pulverizing with a pulverizer equipped with a 100 - 120 mesh sieve screen for 1 - 2 times.

[0014] In some embodiments of the present invention, when the number of crushing times is 1 time, the mesh size of the crusher screen can be selected from 100 mesh, 105 mesh, 110 mesh, 115 mesh or 120 mesh; when the number of crushing times is 2 times, the mesh sizes of the two crushing screens can be independently selected from 100 mesh, 105 mesh, 110 mesh, 115 mesh or 120 mesh.

[0015] Preferably, the powdered API is obtained by pulverizing once in a pulverizer with a built-in 100-mesh screen.

[0016] In some embodiments of the present invention, the powdered API is obtained by pulverizing twice using a pulverizer with a built-in 80-mesh screen.

[0017] Furthermore, the medicine also includes: raw materials used as medicine in the form of clear paste, including: turtle shell, deer antler, tortoise shell, ganoderma lucidum, snake gall, dendrobium, cordyceps sinensis, saffron and seahorse.

[0018] Furthermore, the raw materials are, by weight, 16.5-62.7 parts of turtle shell, 1.65-16.5 parts of deer antler, 26.4-75.9 parts of tortoise shell, 3.3-29.7 parts of ganoderma lucidum, 1.65-16.5 parts of snake gall, 9.9-42.1 parts of dendrobium, 1.65-14.9 parts of cordyceps, 2.48-22.3 parts of saffron and 2.48-22.3 parts of seahorse.

[0019] American ginseng, Panax notoginseng, Schisandra chinensis, Salvia miltiorrhiza, Chicken's gizzard lining, Dendrobium candidum, Cordyceps sinensis, Saffron, Seahorse, Turtle shell, Deer antler, Tortoise shell (also known as tortoise shell) and Ganoderma lucidum, the above medicinal materials' origins, medicinal parts, properties, flavors, meridians, and efficacy all comply with the corresponding provisions of the Part 1 of the 2020 edition of the Chinese Pharmacopoeia.

[0020] The medicinal origin, medicinal parts, properties, flavors, meridians, and efficacy of snake gall are all in line with the relevant provisions of the 2012 edition of "Fujian Province Traditional Chinese Medicine Preparation Specifications".

[0021] The second object of the present invention is:

[0022] A method for preparing any of the above-mentioned drugs is provided, comprising the following steps:

[0023] (1) Weigh the raw materials American ginseng, Panax notoginseng, Schisandra chinensis, Salvia miltiorrhiza, Gallus galli, Dendrobium officinale, Cordyceps sinensis, Saffron and Hippocampus;

[0024] (2) Grinding process: Grinding each API to obtain the corresponding API powder;

[0025] (3) Mixing process: mixing the raw material powders obtained in step (2) to obtain powdered raw material medicine;

[0026] (4) The crude drug for making the extract is decocted with water. The decoction is concentrated and then mixed with the powdered crude drug, followed by spherical pelletization, drying, coating and polishing to obtain the product.

[0027] In some embodiments of the present invention, the pulverization process uses a turbo mill; the mixing process uses a three-dimensional motion high-efficiency mixer. The blower speed regulation of the pulverization process is 40 - 50 Hz, and the feeder speed regulation is 8 - 25 Hz.

[0028] In the mixing process, the mixing rotation speed is 10 - 12 revolutions per minute.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] (1) By optimizing and improving the pulverization process of the medicinal materials in powder form in Yi'anning Pills, that is, by setting a sieve with a specific mesh number to pulverize the crude drug and regulating the pulverization times, the present invention realizes the control of the particle size of the crude drug powder; in this preparation process, when the crude drug powder is within a specific particle size range (D90 is 125 - 145 μm, D50 is 50 - 100 μm, D10 is 18 - 35 μm), not only the mixing uniformity of the effective active ingredients of the drug is improved, but also the fluidity of the drug powder is improved;

[0031] (2) The preparation process of the present invention not only makes the mixing uniformity of the drug meet the relevant standard requirements, but also shortens the mixing time to reach the standard mixing uniformity, improves the production efficiency, and can be used for large-scale production;

[0032] (3) The drug prepared by the present invention has excellent comprehensive performance, provides a guarantee for the subsequent preparation and quality control of Yi'anning Pills, and has a wide application prospect. Description of the Drawings

[0033] Figure 1 Chromatograms of notoginsenoside R1 and ginsenoside Rb1 in the blank solution for the determination of mixing uniformity;

[0034] Figure 2 Chromatograms of notoginsenoside R1 and ginsenoside Rb1 in the reference substance mixed solution for the determination of mixing uniformity;

[0035] Figure 3 Chromatograms of notoginsenoside R1 and ginsenoside Rb1 in the sample solution of Test Sample 1 - 1 at 30 minutes for the determination of mixing uniformity;

[0036] Figure 4 Chromatogram of salvianolic acid B in the blank solution for the determination of mixing uniformity;

[0037] Figure 5 Chromatogram of salvianolic acid B in the reference substance solution for the determination of mixing uniformity;

[0038] Figure 6 It is the chromatogram of salvianolic acid B at 30 minutes of the sample solution of Test Article 1-1 in the determination of mixing uniformity. Detailed implementation manners

[0039] The following non-limiting examples can enable those of ordinary skill in the art to understand the present invention more comprehensively, but do not limit the present invention in any way. The following content is only an exemplary illustration of the scope claimed by the present invention. Those skilled in the art can make various changes and modifications to the invention of the present invention based on the disclosed content, and it should also fall within the scope claimed by the present invention.

[0040] Reference substances ginsenoside Rb1 (batch number: 110704-202331; content 93.8%), notoginsenoside R1 (batch number: 110745-202322; content 97.8%), and salvianolic acid B (batch number 111562-201917; content 96.6%) were all purchased from the National Institutes for Food and Drug Control.

[0041] Example 1

[0042] The drug formula for treating coronary heart disease is as follows:

[0043] Powder raw materials: 10 parts of American ginseng, 8 parts of notoginseng, 2 parts of schisandra, 2 parts of salvia miltiorrhiza, 2 parts of chicken gizzard-membrane, 1.6 parts of dendrobium, 1.6 parts of cordyceps sinensis, 0.8 part of saffron, and 0.8 part of hippocampus;

[0044] Extract raw materials: 8 parts of turtle shell, 2.6 parts of pilose antler, 10 parts of tortoise plastron, 3.2 parts of ganoderma lucidum, 2 parts of snake gallbladder, 5 parts of dendrobium, 1.6 parts of cordyceps sinensis, 2.4 parts of saffron, and 2.4 parts of hippocampus.

[0045] The preparation process is as follows:

[0046] (1) Crushing of powder raw materials: Respectively take the above-mentioned prescription herbs, use a turbo mill, set the blower speed to 50 Hz, the feeder speed to 10 Hz, with an 80-mesh sieve inside the mill, crush once, and stop crushing when the sound of the mill shows an idling sound for about 2 minutes; then pass the crushed drug through an 80-mesh sieve using a high-efficiency sieve powder machine, collect the sieved drug, and obtain the corresponding raw material powder; mix the above-mentioned raw material powder using a three-dimensional motion high-efficiency mixer, with the mixer speed at 10 revolutions per minute, and mix thoroughly for 60 minutes to obtain powder raw material 1;

[0047] (2) Preparation of extract: Take the above-mentioned prescription herbs and decoct them twice with water. Use 8 times the amount of water for the first time and 6 times the amount of water for the second time, each decocting for 2 hours. Combine the decoction liquids, filter, and concentrate to an extract with a relative density of 1.20-1.22 (measured at 70°C);

[0048] (3) Mix the clear extract with the powdered raw drug 1, make pills by using honey and adding water, dry, coat and polish to obtain the product.

[0049] Example 2

[0050] The drug formula is the same as that in Example 1.

[0051] The preparation method is different from that in Example 1 only in that: it is pulverized twice. When pulverizing for the first time, the built-in sieve of the pulverizer is 80 mesh, and when pulverizing for the second time, the built-in sieve is 100 mesh. After pulverizing and mixing, the powdered raw drug 2 is obtained; other steps are the same as those in Example 1.

[0052] Example 3

[0053] The drug formula is the same as that in Example 1.

[0054] The preparation method is different from that in Example 1 only in that: the built-in sieve of the pulverizer is 100 mesh. After pulverizing and mixing, the powdered raw drug 3 is obtained; other steps are the same as those in Example 1.

[0055] Example 4

[0056] The drug formula is the same as that in Example 1.

[0057] The preparation method is different from that in Example 1 only in that: it is pulverized twice. When pulverizing for the first time, the built-in sieve of the pulverizer is 100 mesh, and when pulverizing for the second time, the built-in sieve is 120 mesh. After pulverizing and mixing, the powdered raw drug 4 is obtained; other steps are the same as those in Example 1.

[0058] Example 5

[0059] The drug formula is the same as that in Example 1.

[0060] The preparation method is different from that in Example 1 only in that: the built-in sieve of the pulverizer is 120 mesh. After pulverizing and mixing, the powdered raw drug 5 is obtained; other steps are the same as those in Example 1.

[0061] Example 6

[0062] The drug formula is the same as that in Example 1.

[0063] The preparation method is different from that in Example 1 only in that: the built-in sieve of the pulverizer is 150 mesh. After pulverizing and mixing, the powdered raw drug 6 is obtained; other steps are the same as those in Example 1.

[0064] Test Example

[0065] I. Test method:

[0066] (1) Mixing uniformity:

[0067] (1-1) Sampling: Samples were taken at 10 minutes, 20 minutes, 30 minutes, 45 minutes, and 60 minutes after mixing respectively. After stopping the machine at each sampling time point, open the upper cover of the three-dimensional motion mixer, and use a GTD-D type fixed-point metering sampling probe to sample at three layers in the three-dimensional motion mixer, namely the upper layer, the middle layer, and the discharge port. For the upper layer, sample at 5 points along the cross, including 4 points near the mixer wall in the front, back, left, and right directions and the cross center point (sample three times at each point). The corresponding sample numbers for each sampling point are sample 1-1, sample 1-2, sample 1-3, sample 2-1, sample 2-2, sample 2-3, sample 3-1, sample 3-2, sample 3-3, sample 4-1, sample 4-2, sample 4-3, sample 5-1, sample 5-2, sample 5-3; for the middle layer, sample at 5 points along the cross, including 4 sampling points near the inner wall of the mixer in the front, back, left, and right directions and the cross center point. The corresponding sample numbers for each sampling point are sample 6-1, sample 6-2, sample 6-3, sample 7-1, sample 7-2, sample 7-3, sample 8-1, sample 8-2, sample 8-3, sample 9-1, sample 9-2, sample 9-3, sample 10-1, sample 10-2, sample 10-3; for the discharge port, sample at the center point, and the corresponding sample numbers are sample 11-1, sample 11-2, sample 11-3. Quantitatively take 1 g from each sampling point for detecting the content of the common component ginsenoside Rb1 in American ginseng and notoginseng and the content of the unique component notoginsenoside R1 in notoginseng. Take 2 g from each sampling point for determining the content of the unique component salvianolic acid B in salvia miltiorrhiza.

[0068] (1-2) Testing:

[0069] ① Method for determining the content of the common component ginsenoside Rb1 in American ginseng and notoginseng and the content of the unique component notoginsenoside R1 in notoginseng:

[0070] Use a Venusil XBP C18 chromatographic column (4.6×250 mm, 5 μm), with octadecylsilane-bonded silica gel as the filler; use acetonitrile as mobile phase A and water as mobile phase B, and perform gradient elution according to the regulations in the following table (the elution program is shown in Table 1); the detection wavelength is 203 nm; the theoretical plate number should be not less than 4000 calculated by the notoginsenoside R1 peak and not less than 5000 calculated by the ginsenoside Rb1 peak.

[0071] Table 1 Elution Program

[0072]

[0073] Preparation of the reference substance solution: Weigh accurately appropriate amounts of ginsenoside Rb1 and notoginsenoside R1 reference substances, add methanol to make a mixed solution containing 0.4 mg of ginsenoside Rb1 and 0.1 mg of notoginsenoside R1 per 1 mL, and that's it.

[0074] Preparation of test solution: Weigh 1.0 g of each of the above sampled samples accurately, add 50 mL of methanol accurately, weigh, let stand overnight, keep on a water bath at 80 °C and maintain gentle boiling for 2 hours, cool, weigh again, make up the lost weight with methanol, shake well, filter, and take the subsequent filtrate to obtain the test solution.

[0075] Assay method: Accurately pipette 10 μL each of the blank solvent, reference solution and test solution, inject into the liquid chromatograph for determination. The results are shown in Figures 1-3 (wherein the blank solvent is methanol and the test solution is sample 1-1 of the powdered bulk drug 1).

[0076] Determine one sample at each sampling point, calculate the RSD value of the salvianolic acid B content at 11 sampling points to evaluate the mixing uniformity of each drug. If the RSD value is greater than 5%, then detect the remaining 2 samples at each sampling point, calculate the RSD value of the ginsenoside Rb1 content and notoginsenoside R1 content of all the detected samples to evaluate the mixing uniformity of each drug.

[0077] ② Determination method for the content of salvianolic acid B, a unique component of Salvia miltiorrhiza:

[0078] Use a Diamonsil Plus 5um C18 chromatographic column (4.6×250mm, 5μm), with octadecylsilyl-bonded silica gel as the filler; use acetonitrile - 0.1% phosphoric acid solution (22:78) as the mobile phase for isocratic elution; the column temperature is 25 °C; the flow rate is 1.0 ml per minute; the detection wavelength is 286 nm; the number of theoretical plates calculated based on the salvianolic acid B peak should be not less than 6000.

[0079] Preparation of reference solution: Take an appropriate amount of salvianolic acid B reference substance, weigh accurately, and prepare a solution containing 0.10 mg per 1 ml with a methanol - water (8:2) mixed solution to obtain the reference solution.

[0080] Preparation of test solution: Weigh 2.0 g of each of the above sampled samples accurately, place in a stoppered conical flask, add 50 ml of methanol - water (8:2) mixed solution accurately, stopper tightly, weigh, ultrasonically treat (power 140 W, frequency 42 kHz) for 30 minutes, cool, weigh again, make up the lost weight with methanol - water (8:2) mixed solution, shake well, filter, accurately measure 5 ml of the subsequent filtrate, transfer to a 10 ml volumetric flask, dilute to the mark with methanol - water (8:2) mixed solution, shake well, filter, and take the subsequent filtrate to obtain the test solution.

[0081] Assay method: Accurately pipette 10 μL each of the blank solvent, reference solution and test solution, inject into the liquid chromatograph for determination. The results are shown in Figures 4-6 (wherein the blank solvent is methanol - water (8:2) mixed solution and the test solution is sample 1-1 of the powdered bulk drug 1).

[0082] One sample is measured at each sampling point, and the RSD value of the salvianolic acid B content at 11 sampling points is calculated to evaluate the mixing uniformity of each drug. If the RSD value is greater than 5%, the remaining 2 samples at each sampling point are tested, and the RSD value of the salvianolic acid B content of all the tested samples is calculated to evaluate the mixing uniformity of each drug.

[0083] (2) Particle size distribution:

[0084] (2-1) Sampling: After mixing, use a GTD-D type fixed-point metering sampling probe to take 20 g of samples at each sampling point in the upper layer, middle layer and discharge port of the powdered API, a total of 220 g of samples. Place them in a 500-ml stoppered sample bottle, tightly cover the lid, invert and turn it upside down 50 times to mix evenly. Use a sampling spoon to take 1 spoonful of sample at 4 sampling points near the bottle wall in the front, back, left and right directions along the cross direction in the upper layer and 1 sampling point at the center of the bottle, place it in the sample bottle, invert and turn it upside down 50 times to mix evenly, and then send the sample for particle size distribution measurement.

[0085] (2-2) Testing: Use a Topsizer Omec laser particle size analyzer to perform dry measurement. The dispersing medium is air, the background sampling time is 12 seconds, and the sample sampling time is 12 seconds. The particle size distributions of 6 kinds of powdered APIs are detected respectively, and the D90, D50, and D10 particle size ranges of each powdered API are measured. The results are shown in Table 8.

[0086] (3) Powder flowability: Take the remaining samples of 6 kinds of powdered APIs after taking the samples for particle size distribution measurement for measuring the powder flowability. The measurement method follows the "Guidelines for Measuring Powder Flowability" issued by the National Pharmacopoeia Commission, and the angle of repose of 6 drugs is measured by the funnel method. The results are shown in Table 8.

[0087] II. Test results:

[0088] The measurement results of the mixing uniformity at 11 sampling points of 6 kinds of powdered APIs at different mixing times are shown in Table 2-7.

[0089] Table 2 Measurement results of the mixing uniformity at 11 sampling points of powdered API 1 at different mixing times

[0090]

[0091] Table 3 Measurement results of the mixing uniformity at 11 sampling points of powdered API 2 at different mixing times

[0092]

[0093] Table 4 Results of the determination of mixing uniformity at 11 sampling points for Powder API 3 at different mixing times

[0094]

[0095]

[0096] Table 5 Results of the determination of mixing uniformity at 11 sampling points for Powder API 4 at different mixing times

[0097]

[0098]

[0099] Table 6 Results of the determination of mixing uniformity at 11 sampling points for Powder API 5 at different mixing times

[0100]

[0101]

[0102] Table 7 Results of the determination of mixing uniformity at 11 sampling points for Powder API 6 at different mixing times

[0103]

[0104]

[0105] As can be seen from Table 2 to Table 7, the mixing times required for the powder APIs prepared by different comminution processes to meet the specified standards (relative deviation RSD of the content of the detected components at each sampling point ≤ 5%) for each index to be measured (ginsenoside Rb1, notoginsenoside R1, and salvianolic acid B) are different. Among them, Powder APIs 1 - 4 can all meet the requirements within 30 minutes; Powder API 5 is close to the upper limit of the standard requirement of 5% at 60 minutes, with a risk of non - compliance; Powder API 6 still does not meet the requirements at 60 minutes, and the mixing uniformity does not meet the regulations. Therefore, from the perspective of mixing uniformity, when the built - in screen mesh has a relatively large mesh number in the comminution process, the mixing uniformity of the drug cannot meet the requirements, or the mixing time required to meet the requirements is relatively long.

[0106] Table 8 Summary of the determination results of mixing uniformity, particle size distribution, and flowability repose angle for Powder APIs 1 - 6

[0107]

[0108]

[0109] The particle size distribution results in Table 8 also verify the above conclusion, that is, as the comminution particle size of each medicinal flavor in the powdered API decreases, the time required for its mixing to reach the specified mixing uniformity is longer. For example, when the particle size of the drug is D90 = 61.219 μm, D50 = 18.427 μm, and D10 = 6.712 μm, that is, for powdered API 6, the mixing time using a three-dimensional motion mixer is as long as 60 minutes. The mixing uniformity determination results with the common components of American ginseng and notoginseng, ginsenoside Rb1, the unique component of notoginseng, notoginsenoside R1, and the unique component of salvia miltiorrhiza, salvianolic acid B as the index components show that the RSD of the contents of the three index components of the samples taken at 11 sampling points all exceed 5%, and the mixing uniformity does not meet the requirements. The particle size of powdered API 5 is slightly coarser than that of powdered API 6. Although after 60 minutes of mixing, the RSD of the mixing uniformity of the three index components is less than 5%, the mixing time required is too long, and the RSD of the uniformity of the three index components is close to the upper limit value of 5%, presenting a risk of non-compliance.

[0110] In addition, from the perspective of the angle of repose of the medicinal powder, the smaller the comminution particle size of each medicinal flavor in the drug, the larger the angle of repose of the medicinal powder, and the worse the fluidity of the powder. When the particle size distribution of the medicinal powder is D90 = 61.219 μm, D50 = 18.427 μm, and D10 = 6.712 μm, that is, for powdered API 6, the angle of repose is as high as 56.26°, and the fluidity is very poor; the angle of repose of powdered API 5 exceeds 40°, and it also belongs to the powder with poor fluidity. Considering fluidity, obviously neither of them is suitable for the preparation of subsequent oral preparations such as pills.

[0111] Among the 6 kinds of powdered APIs prepared in the examples of the present invention, the powdered APIs 3 and 4 have a short mixing uniformity compliance time and a small angle of repose of the medicinal powder, belonging to the category of excellent fluidity. The particle sizes of powdered APIs 1 and 2 are relatively large, and their mixing uniformity can also meet the standards after 30 minutes of mixing. However, the D90 and D50 of API 1 are relatively large, and the proportion of coarse particles is large, which further leads to an increase in the RSD of the mixing uniformity content deviation of the three index components of the samples taken at 11 sampling points (compared with powdered APIs 2 - 4). Further extending the mixing time, the RSD value of the mixing uniformity does not decrease significantly. This shows that too large a particle size and too many coarse powders of the powdered API are also not conducive to the uniformity of the finished product content.

[0112] In summary, among the 6 kinds of powdered APIs prepared in the present invention, the powdered APIs 2, 3, and 4 have a more optimal particle size distribution, the best mixing uniformity, a moderate mixing uniformity compliance time, and good fluidity of the medicinal powder, providing a guarantee for the quality uniformity of the subsequent Yianning Pills and the stability of clinical efficacy.

[0113] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than a limitation on the protection scope of the present invention. Any simple modification or equivalent replacement made by those of ordinary skill in the art to the technical solution of the present invention shall not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing a drug for treating coronary heart disease, characterized in that: The following steps are involved: (1) Weigh the raw materials American ginseng, Panax notoginseng, Schisandra chinensis, Salvia miltiorrhiza, Gallus galli, Dendrobium officinale, Cordyceps sinensis, Saffron and Seahorse; (2) Grinding process: Grinding each API to obtain the corresponding API powder; (3) Mixing process: mixing the raw material powders obtained in step (2) to obtain powdered raw material medicine; (4) Take the raw material drug for the clear paste and boil it with water. After the decoction is concentrated, mix it with the powdered raw material drug, make pills, dry, coat and polish them, and the product is obtained. The medicine is prepared from raw material powder used as medicine in powder form and raw material powder used as medicine in clear paste form, wherein the raw material powder used as medicine in powder form comprises, by weight, 26.4-75.9 parts of American ginseng, 16.5-62.7 parts of Panax notoginseng, 1.65-16.5 parts of Schisandra chinensis, 1.65-26.4 parts of Salvia miltiorrhiza, 1.65-16.5 parts of Gallus gallus domesticus, 3.3-14.0 parts of Dendrobium officinale, 1.65-14.9 parts of Cordyceps sinensis, 0.82-7.42 parts of Crocus saffron and 0.82-7.42 parts of Hippocampus; The raw materials used in the clear paste are, by weight, 16.5-62.7 parts of turtle shell, 1.65-16.5 parts of deer antler, 26.4-75.9 parts of tortoise shell, 3.3-29.7 parts of ganoderma lucidum, 1.65-16.5 parts of snake gall, 9.9-42.1 parts of dendrobium, 1.65-14.9 parts of cordyceps, 2.48-22.3 parts of saffron and 2.48-22.3 parts of seahorse; The particle size range of the powdered API is: D90 is 125-145 μm, D50 is 50-100 μm, and D10 is 18-35 μm; The raw material powder for use as powder medicine is obtained by crushing 1-2 times using a crusher with a built-in 100-mesh screen; the mixing is carried out using a three-dimensional motion high-efficiency mixer with a mixing speed of 10-12 revolutions per minute.

2. The preparation method according to claim 1, characterized in that: The raw material powder is obtained by pulverizing once using a pulverizer with a built-in 100-mesh screen.

3. A method for preparing a drug for treating coronary heart disease, characterized in that: The following steps are involved: (1) Weigh the raw materials American ginseng, Panax notoginseng, Schisandra chinensis, Salvia miltiorrhiza, Gallus galli, Dendrobium officinale, Cordyceps sinensis, Saffron and Seahorse; (2) Grinding process: Grinding each API to obtain the corresponding API powder; (3) Mixing process: mixing the raw material powders obtained in step (2) to obtain powdered raw material medicine; (4) Take the raw material drug for the clear paste and boil it with water. After the decoction is concentrated, mix it with the powdered raw material drug, make pills, dry, coat and polish them, and the product is obtained. The medicine is prepared from raw material powder used as medicine in powder form and raw material powder used as medicine in clear paste form, wherein the raw material powder used as medicine in powder form comprises, by weight, 26.4-75.9 parts of American ginseng, 16.5-62.7 parts of Panax notoginseng, 1.65-16.5 parts of Schisandra chinensis, 1.65-26.4 parts of Salvia miltiorrhiza, 1.65-16.5 parts of Gallus gallus domesticus, 3.3-14.0 parts of Dendrobium officinale, 1.65-14.9 parts of Cordyceps sinensis, 0.82-7.42 parts of Crocus saffron and 0.82-7.42 parts of Hippocampus; The raw materials used in the clear paste are, by weight, 16.5-62.7 parts of turtle shell, 1.65-16.5 parts of deer antler, 26.4-75.9 parts of tortoise shell, 3.3-29.7 parts of ganoderma lucidum, 1.65-16.5 parts of snake gall, 9.9-42.1 parts of dendrobium, 1.65-14.9 parts of cordyceps, 2.48-22.3 parts of saffron and 2.48-22.3 parts of seahorse; The particle size range of the powdered API is: D90 is 125-145 μm, D50 is 50-100 μm, and D10 is 18-35 μm; The raw material powder for use as powder medicine is obtained by pulverizing twice using a pulverizer with a built-in 80-mesh screen and a pulverizer with a built-in 100-mesh screen; the mixing is performed using a three-dimensional motion high-efficiency mixer with a mixing speed of 10-12 revolutions per minute.

4. A method for preparing a drug for treating coronary heart disease, characterized in that: The following steps are involved: (1) Weigh the raw materials American ginseng, Panax notoginseng, Schisandra chinensis, Salvia miltiorrhiza, Gallus galli, Dendrobium officinale, Cordyceps sinensis, Saffron and Seahorse; (2) Grinding process: Grinding each API to obtain the corresponding API powder; (3) Mixing process: mixing the raw material powders obtained in step (2) to obtain powdered raw material medicine; (4) Take the raw material drug for the clear paste and boil it with water. After the decoction is concentrated, mix it with the powdered raw material drug, make pills, dry, coat and polish them, and the product is obtained. The medicine is prepared from raw material powder used as medicine in powder form and raw material powder used as medicine in clear paste form, wherein the raw material powder used as medicine in powder form comprises, by weight, 26.4-75.9 parts of American ginseng, 16.5-62.7 parts of Panax notoginseng, 1.65-16.5 parts of Schisandra chinensis, 1.65-26.4 parts of Salvia miltiorrhiza, 1.65-16.5 parts of Gallus gallus domesticus, 3.3-14.0 parts of Dendrobium officinale, 1.65-14.9 parts of Cordyceps sinensis, 0.82-7.42 parts of Crocus saffron and 0.82-7.42 parts of Hippocampus; The raw materials used in the clear paste are, by weight, 16.5-62.7 parts of turtle shell, 1.65-16.5 parts of deer antler, 26.4-75.9 parts of tortoise shell, 3.3-29.7 parts of ganoderma lucidum, 1.65-16.5 parts of snake gall, 9.9-42.1 parts of dendrobium, 1.65-14.9 parts of cordyceps, 2.48-22.3 parts of saffron and 2.48-22.3 parts of seahorse; The particle size range of the powdered API is: D90 is 125-145 μm, D50 is 50-100 μm, and D10 is 18-35 μm; The raw material powder for use as powder medicine is obtained by pulverizing twice using a pulverizer with a built-in 100-mesh screen and a pulverizer with a built-in 120-mesh screen; the mixing is performed using a three-dimensional motion high-efficiency mixer with a mixing speed of 10-12 revolutions per minute.

5. The preparation method according to any one of claims 1 to 4, characterized in that: The raw material powders are 10 parts of American ginseng, 8 parts of Panax notoginseng, 2 parts of Schisandra chinensis, 2 parts of Salvia miltiorrhiza, 2 parts of Chicken's gizzard lining, 1.6 parts of Dendrobium, 1.6 parts of Cordyceps sinensis, 0.8 parts of Saffron and 0.8 parts of Seahorse in parts by weight.

6. The preparation method according to any one of claims 1 to 4, characterized in that: The fan speed of the pulverizing process is adjusted to 40-50 Hz, and the feeder speed is adjusted to 8-25 Hz.

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