Preparation method of Shenqi kidney-regulating compound granules

Abstract

The invention discloses a preparation method of Shenqi kidney-regulating compound granules, and relates to the technical field of traditional Chinese medicine preparations. According to the invention, a proper extraction process is selected, so that the raw medicinal materials have a relatively high ointment yield, and the obtained Shenqi kidney-regulating formula compound granules simultaneously contain relatively high contents of effective components, namely ginsenoside Rg1 and calycosin-7-glucoside, so that the bioavailability of the medicinal components is improved, and the curative effect is remarkable.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine preparations, and in particular to a method for preparing granules of Shenqi Tiaoshen prescription compound. Background Art

[0002] Chronic obstructive pulmonary disease (COPD) has a high prevalence, disability rate and mortality rate, and has become the fourth most fatal disease in my country. Shenqi Tiaoshen Fang is a standard decoction based on the principle of tonifying both the lung and kidney, strengthening the body and removing blood stasis, and improving the symptoms of "lung and kidney deficiency". Preliminary clinical observations have found that this prescription can effectively improve the clinical symptoms of COPD patients with lung and kidney deficiency, reduce the number of acute exacerbations, delay the decline of lung function, improve exercise tolerance and quality of life, and its efficacy is definite. Chinese medicine granules are stable in nature, easy to transport and store, and easy to achieve large-scale production. However, when preparing them, the effective ingredients of Chinese medicinal materials need to be extracted first, and then a series of processes such as concentration, drying, and granulation are used to obtain the products. During the extraction process, the effective ingredients in the medicinal materials are often not well retained, thus affecting the efficacy. Therefore, it is necessary to develop a compound granule of Shenqi Tiaoshen Fang that can well retain the effective ingredients and has significant efficacy. Summary of the invention

[0003] Based on the technical problems existing in the background technology, the present invention proposes a preparation method of Shenqi Tiaoshen compound granules.

[0004] The present invention provides a method for preparing Shenqi Tiaoshen Fang compound granules, comprising the following steps:

[0005] S1. Weigh the raw materials according to the following formula: 10g ginseng, 20g roasted astragalus, 10g oxyphylla, 3g cinnamon, 6g polygonatum, 6g tangerine peel, 12g cornus, 10g peach kernel, 6g white mustard seed; after mixing the above raw materials, add water equivalent to 12 times the total weight of the raw materials, fully soak, then decoct for 120min, filter after cooling, add water equivalent to 12 times the total weight of the raw materials to the filter cake, decoct for 120min, combine the filtrate obtained by the two decoctions, concentrate under reduced pressure, and then freeze-dry to obtain a Chinese medicine paste powder;

[0006] S2. After mixing the Chinese medicine paste powder with auxiliary materials, dry granulation is performed to obtain the Shenqi Tiaoshen Formula compound granules.

[0007] Preferably, in S1, the soaking time is 1 to 2 hours.

[0008] Preferably, in S1, the temperature of the reduced pressure concentration is 50-80°C.

[0009] Preferably, in S2, the auxiliary material includes a filler, and the weight of the filler is 20 to 80% of the weight of the traditional Chinese medicine ointment powder.

[0010] Preferably, the filler is selected from soluble starch, maltodextrin or a combination thereof.

[0011] Preferably, the adjuvant includes a lubricant, and the weight of the lubricant is 0.1-0.5% of the weight of the traditional Chinese medicine paste powder.

[0012] Preferably, the lubricant is selected from at least one of magnesium stearate, talc powder, and polyethylene glycol.

[0013] The present invention also provides a Shenqi Tiaoshen formula compound granule prepared by the preparation method described above.

[0014] The beneficial effects of the present invention are as follows:

[0015] The present invention selects a suitable extraction process, which enables the raw medicinal materials to have a high paste yield, and enables the obtained Shenqi Tiaoshen formula compound granule to contain a high content of the active ingredients ginsenoside Rg1 and calycosin-7-O-β-D-glucoside at the same time, improving the bioavailability of the drug ingredients and having a significant curative effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is the liquid chromatogram of the test solution for detecting ginsenoside Rg1 of the present invention.

[0017] Figure 2 It is the liquid chromatogram of the reference solution for detecting ginsenoside Rg1 of the present invention.

[0018] Figure 3 It is the standard curve graph for detecting the content of ginsenoside Rg1 of the present invention.

[0019] Figure 4 It is the liquid chromatogram of the test solution for detecting calycosin-7-O-β-D-glucoside of the present invention.

[0020] Figure 5 It is the liquid chromatogram of the reference solution for detecting calycosin-7-O-β-D-glucoside of the present invention.

[0021] Figure 6 It is the standard curve graph for detecting the content of calycosin-7-O-β-D-glucoside of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0022] Next, the technical solutions of the present invention will be described in detail through specific examples.

[0023] Example 1 Optimization of the Extraction Process

[0024] According to the formula of Shenqi Tiaoshen Fang, the raw materials were weighed and water-decocted to prepare the Chinese medicine paste powder. The specific process is as follows: after mixing the raw materials, add appropriate amount of water, fully soak, and then decoct, concentrate the filtrate obtained by decoction, and then freeze-dry to obtain the Chinese medicine paste powder; in order to select the best extraction process, an orthogonal experiment was designed, and the amount of water added for each decoction extraction (times), the time for each decoction extraction (min), the number of decoction extractions (times) and the concentration method were used as influencing factors for investigation. The orthogonal table is shown in Table 1:

[0025] Table 1

[0026]

[0027] Determination of ginsenoside Rg1 content in traditional Chinese medicine ointment powder: According to the content determination method of the Pharmacopoeia of the People's Republic of China (2020 Edition), chromatographic analysis was performed using a high performance liquid chromatograph to determine the peak area. See Table 2 for the chromatographic conditions for the determination of ginsenoside Rg1: octadecylsilane bonded silica gel as filler; acetonitrile-water solution as mobile phase, acetonitrile as mobile phase A, and water as mobile phase B; detection wavelength of 203nm; flow rate of 1.0mL / min; column temperature of 30°C; injection volume of 10μL. The number of theoretical plates calculated based on the ginsenoside Rg1 peak should not be less than 6000.

[0028] Table 2: Chromatographic conditions for ginsenosides

[0029]

[0030] Preparation of ginsenoside Rg1 test solution:

[0031] Accurately weigh 0.25 mg (accurate to 0.001 g) of Chinese medicine paste powder, add 10 mL of 50% methanol, ultrasonicate for 30 minutes, make up the weight, let stand, filter, take the filtrate, pass the filtrate through a 0.22 μm microporous filter membrane, and set aside.

[0032] Preparation of ginsenoside Rg1 reference solution:

[0033] Accurately weigh the ginsenoside Rg1 reference substance, add methanol to make a solution containing 0.13 mg of ginsenoside Rg1 per 1 mL.

[0034] Under the above chromatographic conditions, chromatographic analysis of the ginsenoside Rg1 test solution and the reference solution was performed using a high performance liquid chromatograph. The results are as follows: Figure 1 , Figure 2 shown.

[0035] Preparation of standard curve of ginsenoside Rg1:

[0036] Precisely measure the stock solution of the reference substance solution of ginsenoside Rg1, and dilute it with pure methanol to obtain a series of solutions with concentrations of 0.008125, 0.01625, 0.0325, 0.065, 0.0975, and 0.13 g / mL respectively. Detect and plot the standard curve according to the chromatographic conditions of ginsenoside Rg1 above, and the obtained standard curve is as Figure 3 shown. Taking the concentration of ginsenoside Rg1 as the abscissa (x) and the peak area as the ordinate (y) for linear regression, the linear equation is y = 50.235x + 0.0774 (R 2 = 0.9993), indicating that ginsenoside Rg1 has a good linear relationship in the range of 0.008125 - 0.13 μg / mL.

[0037] Determination of the content of calycosin - 7 - O - glucoside in traditional Chinese medicine paste powder: According to the content determination method in "Pharmacopoeia of the People's Republic of China (2020 Edition)", use a high - performance liquid chromatograph for chromatographic analysis and measure the peak area. The chromatographic conditions for the determination of calycosin - 7 - O - glucoside are shown in Table 3: Using octadecylsilane chemically bonded silica gel as the filler; using acetonitrile as mobile phase A and 0.2% formic acid solution as mobile phase B, and perform gradient elution according to the regulations in the following table; the detection wavelength is 260 nm. The injection volume is 10 μL. The number of theoretical plates calculated based on the calycosin - 7 - O - glucoside peak should be not less than 3000.

[0038] Table 3

[0039]

[0040] Preparation of the test solution of calycosin - 7 - O - glucoside:

[0041] Accurately weigh 0.25 mg of traditional Chinese medicine paste powder (accurate to 0.001 g), add 25 mL of 50% methanol, ultrasonicate for 30 minutes, make up the weight, let it stand, filter, take the subsequent filtrate, and pass the subsequent filtrate through a 0.22 - μm microporous filter membrane for standby.

[0042] Preparation of the reference substance solution of calycosin - 7 - O - glucoside:

[0043] Precisely weigh the reference substance of calycosin - 7 - O - glucoside, add methanol to make a solution containing 0.2 mg of calycosin - 7 - O - glucoside per 1 mL, and that's it.

[0044] Under the above - mentioned chromatographic conditions, use a high - performance liquid chromatograph to perform chromatographic analysis on the test solution and reference substance solution of calycosin - 7 - O - glucoside, and the results are as Figure 4 、 Figure 5 shown.

[0045] Making the standard curve of calycosin - 7 - O - glucoside:

[0046] Precisely measure the stock solution of calycosin-7-O-β-D-glucoside reference substance solution, and dilute it with pure methanol to obtain a series of solutions with concentrations of 0.0125, 0.025, 0.05, 0.1, 0.15, and 0.2 g / mL respectively. Detect and plot the standard curve according to the chromatographic conditions of calycosin-7-O-β-D-glucoside mentioned above. The obtained standard curve is as Figure 6 shown. Using the calycosin-7-O-β-D-glucoside concentration as the abscissa (x) and the peak area as the ordinate (y) for linear regression, the linear equation is y = 472.45x + 0.1242 (R 2 = 0.9991), indicating that calycosin-7-O-β-D-glucoside has a good linear relationship in the range of 0.008125 - 0.13 μg / mL.

[0047] Determine the contents of ginsenoside Rg1 and calycosin-7-O-β-D-glucoside in the traditional Chinese medicine paste powder by the above method, and calculate the transfer rates of ginsenoside Rg1 and calycosin-7-O-β-D-glucoside. It is stipulated that the weight coefficient of the dry extract ratio is 0.5, and the weight coefficients of the transfer rates of ginsenoside Rg1 and calycosin-7-O-β-D-glucoside are 0.25 each for comprehensive scoring. The calculation formula is: Comprehensive score = [((Transfer rate of ginsenoside Rg1 / Maximum transfer rate of ginsenoside Rg1) × 0.25 + (Transfer rate of calycosin-7-O-β-D-glucoside / Maximum transfer rate of calycosin-7-O-β-D-glucoside) × 0.25 + (Dry extract ratio / Maximum dry extract ratio) × 0.5)] × 100. According to this method, the best extraction process is screened. The dry extract ratio, transfer rate of ginsenoside Rg1, transfer rate of calycosin-7-O-β-D-glucoside, and comprehensive score table measured in the above orthogonal experiment are shown in Table 4:

[0048] Table 4

[0049]

[0050] As can be seen from Table 4, the extraction processes of groups 3.1, 5.2, and 9.2 have higher comprehensive scores, indicating that they have a higher dry extract ratio, and the obtained traditional Chinese medicine paste powder contains higher contents of the active ingredients ginsenoside Rg1 and calycosin-7-O-β-D-glucoside at the same time. Among them, the dry extract extraction rate and the content of active ingredients of the extraction process of 9.2 are the highest comprehensively.

[0051] Example 2 Preparation of granules

[0052] Respectively mix the traditional Chinese medicine paste powder prepared from the above groups 3.1, 5.2, and 9.2 with soluble starch equivalent to 50% of the weight of the traditional Chinese medicine paste powder and magnesium stearate equivalent to 0.3% of the weight of the traditional Chinese medicine paste powder, and then perform dry granulation to obtain Shenqi Tiaoshen Fang compound granules 1 - 3. Among them, Shenqi Tiaoshen Fang compound granule 1 corresponds to the traditional Chinese medicine paste powder 3.1, Shenqi Tiaoshen Fang compound granule 2 corresponds to the traditional Chinese medicine paste powder 5.2, and Shenqi Tiaoshen Fang compound granule 3 corresponds to the traditional Chinese medicine paste powder 9.2.

[0053] Pharmacodynamic Test of Example 3

[0054] The pharmacodynamic tests were respectively carried out on the Shenqi Tiaoshen Decoction compound granules 1-3 prepared in Example 2 above. The test method referred to the test method in Example 6 of CN114558049A for the study on the therapeutic effect of Shenqi Tiaoshen Decoction on a rat model of COPD with deficiency of both lung and kidney qi replicated by the method of combining smoking with LPS tracheal instillation, followed by forced swimming and intradermal injection of hydrocortisone. The test subjects were SD rats weighing 180-200 g. They were given drugs by gavage, with the dosage of 14.5 g of crude drug / kg. The continuous drug administration time was 6 weeks. The grasping force and body weight of the rats in the normal group, model group and treatment group were measured before drug administration and after the end of drug administration. The results are shown in Table 5:

[0055] Table 5

[0056]

[0057]

[0058] Note: The drug administration corresponding to Treatment Group 1 was Shenqi Tiaoshen Decoction compound granule 1, the drug administration corresponding to Treatment Group 2 was Shenqi Tiaoshen Decoction compound granule 2, and the drug administration corresponding to Treatment Group 3 was Shenqi Tiaoshen Decoction compound granule 3.

[0059] As can be seen from Table 5, the compound granules prepared by the extraction process with the extraction efficiency of 9.2 have outstanding pharmacodynamic effects. Combining with the extraction effect score in Table 2, it shows that the extraction process of decocting 2 times, with the water addition amount of 12 times for each decoction, the decoction time of 120 min for each decoction, and the concentration method of vacuum concentration can extract the effective components in the raw materials of Shenqi Tiaoshen Decoction to the greatest extent and has significant curative effects.

[0060] The above is only the preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution and inventive concept of the present invention, makes equivalent substitutions or changes, and all should be covered by the protection scope of the present invention.

Claims

1. A preparation method of Shenqi Tiaoshen formula compound granules, characterized in that, The following steps are involved: S1. Weigh the raw materials according to the following formula: 10g ginseng, 20g roasted astragalus, 10g oxyphylla, 3g cinnamon, 6g polygonatum, 6g tangerine peel, 12g cornus, 10g peach kernel, 6g white mustard seed; after mixing the above raw materials, add water equivalent to 12 times the total weight of the raw materials, fully soak, then decoct for 120min, filter after cooling, add water equivalent to 12 times the total weight of the raw materials to the filter cake, decoct for 120min, combine the filtrate obtained by the two decoctions, concentrate under reduced pressure, and then freeze-dry to obtain a Chinese medicine paste powder; S2. After mixing the Chinese medicine paste powder with auxiliary materials, dry granulation is performed to obtain the Shenqi Tiaoshen Formula compound granules.

2. The preparation method of the Shenqi Tiaoshen Formula compound granules according to claim 1, characterized in that, In S1, the soaking time is 1 to 2 hours.

3. The preparation method of the Shenqi Tiaoshen Fang compound granules according to claim 1, characterized in that, In S1, the temperature of the reduced pressure concentration is 50 to 80°C.

4. The preparation method of the Shenqi Tiaoshen Decoction compound granules according to claim 1, wherein In S2, the auxiliary materials include fillers, and the weight of the fillers is 20-80% of the weight of the traditional Chinese medicine ointment powder.

5. The preparation method of the Shenqi Tiaoshen formula compound granules according to claim 4, characterized in that, The filler is selected from soluble starch, maltodextrin or a combination thereof.

6. The preparation method of the Shenqi Tiaoshen formula compound granules according to claim 1, characterized in that, The auxiliary material comprises a lubricant, and the weight of the lubricant is 0.1-0.5% of the weight of the traditional Chinese medicine ointment powder.

7. The preparation method of the Shenqi Tiaoshen formula compound granules according to claim 6, characterized in that, The lubricant is selected from at least one of magnesium stearate, talc and polyethylene glycol.

8. A compound granule of Shenqi Tiaoshen Formula, characterized in that, The invention is prepared by the preparation method according to any one of claims 1 to 7.

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