A preparation method of a daunche capsule

Abstract

The application provides a docusate capsule and a preparation method thereof, which is prepared from the following components in parts by weight: senna 24 parts, angelica 3 parts, cistanche 3 parts, corn starch 1.5-2.0 parts and talc 0.1-0.5 parts. The docusate capsule prepared by the method has significantly improved contents of active ingredients, including sennoside B, ferulic acid and trillin, and is stable in quality after being placed for 6 months.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of traditional Chinese medicine preparations, and relates to a Tongbianling capsule and a preparation method thereof. BACKGROUND

[0002] The Tongbianling capsule is a variety recorded in the seventh volume of the original department standard traditional Chinese medicine formula preparation, is a commonly used traditional Chinese medicine, has the effects of purging heat and removing stagnation, moistening the intestines and relieving constipation, and is clinically used for heat constipation, long-term bedridden constipation, temporary abdominal distension and constipation, and senile habitual constipation. The traditional dosage form and process are as follows: prescription: senna leaf 1200g, angelica 150g, and cistanche 150g; process: 75g of the angelica is crushed into fine powder, the remaining angelica and senna leaf are added with water and decocted for 1.5 hours, filtered, and the filtrate is concentrated into a thick paste, the angelica powder is added, mixed, dried at low temperature, crushed, screened, mixed, and then filled into capsules.

[0003] According to the data of the State Drug Administration, there are about 89 enterprises producing the Tongbianling capsule in 24 provinces in China, and there are more than 20 standards. Since the main component sennoside B is degraded in the solution when extracted at high temperature, the content is significantly reduced, and the treatment effect is also significantly reduced. In addition, because the quality control is relatively simple, the qualitative requirements of more than 20 standards are different, the quantitative indexes are different, the control indexes are different, and the differences are large. Therefore, the effects of the Tongbianling capsules on the market are quite different, and it is urgent to improve them.

[0004] Therefore, it is still necessary to research and develop the prescription and production process of the Tongbianling capsule, improve the quality standard, and ensure the clinical use effect. SUMMARY

[0005] The inventor of the application has long been committed to researching the Tongbianling capsule, and unexpectedly found that the content of active ingredients such as sennoside B, ferulic acid and echinacoside in the Tongbianling capsule is significantly improved by using a specific extraction method, and the treatment effect on constipation is significantly enhanced. The stability is good after being placed under accelerated conditions for 6 months.

[0006] Firstly, the application provides a Tongbianling capsule, which is prepared from the following components in parts by weight:

[0007] Ingredients Parts by weight Senna leaves 24 Angelica 3 Cistanche 3 Corn starch 1.5-2.0 Talc 0.1-0.5

[0008] Further, a Tongbianling capsule is prepared from the following components in parts by weight:

[0009]

[0010]

[0011] Still further, a Tongbianling capsule is prepared from the following components in parts by weight:

[0012] Ingredients Parts by weight Senna leaves 24 Angelica 3 Cistanche 3 Corn starch 1.8 Talc 0.2

[0013] Further, the Tongbianling capsule contains 0.1-0.5g of content per capsule, preferably 0.25g.

[0014] Further, the present application also provides a preparation method of the above-mentioned Tongbianling capsule, comprising the following steps:

[0015] (1) Preparation of Angelica sinensis powder

[0016] ① Cleaning and pretreatment: Angelica sinensis is washed with water for 2-3 times, and the amount of water is 2-3 times of the weight of Angelica sinensis; after cleaning, it is added into 1.8%-2.2% potassium permanganate solution, and the weight of potassium permanganate solution is 2-4 times of the weight of Angelica sinensis, the temperature is controlled at 0-5℃, and stirring is carried out for 1-2h; the temperature is increased to 10-15℃, and stirring is carried out for 2-4h.

[0017] ② Drying: drying under reduced pressure until the moisture content is less than 8.0%.

[0018] ③ Grinding: 50% of the dried Angelica sinensis is ground, and D90 is not more than 120μm, and D50 is not more than 100μm.

[0019] (2) Preparation of extract powder

[0020] ① The remaining Angelica sinensis, senna leaf and cistanche are added with 10-12 times of water, and a composite enzyme composed of cellulase, pectinase and ligninase is added, the pH is adjusted to 4.5-5.5, and extraction is carried out at 50-55℃ for 4-6h, then filtration is carried out, and the filtrate is concentrated into thick paste.

[0021] The weight ratio of cellulase, pectinase and ligninase in the composite enzyme is 1:0.8:0.5; and the weight ratio of the composite enzyme to senna leaf is 0.1-0.3:24.

[0022] ② Drying and grinding: the extract is dried under reduced pressure, and ground, and D90 is not more than 110μm, and D50 is not more than 90μm.

[0023] (3) Preparation of capsule

[0024] ① Pretreatment of talc powder: 20-30% of citrate buffer solution (pH 5.5) of the total amount of talc powder is added to the talc powder, and ball milling is carried out in a ball mill for 1-2h, after ball milling, water washing and drying are carried out, and then it is heated and activated at 90-100℃ for 30min, and then cooled to room temperature.

[0025] ② The Angelica sinensis powder, extract powder, talc powder and corn starch are mixed for 10min, and then loaded into the capsule shell.

[0026] Further, in step (1), preferably 2.0% potassium permanganate solution.

[0027] Further, in step (1), preferably the weight of potassium permanganate solution is 3 times the weight of angelica.

[0028] Further, in step (2), the weight ratio of the composite enzyme to senna leaf is 0.2:24.

[0029] Further, in step (3), preferably 25% citric acid buffer solution.

[0030] Compared with the prior art, the present application has the following beneficial effects:

[0031] (1) The present applicant found that soaking pretreatment of angelica, i.e., soaking angelica with a specific concentration of potassium permanganate solution, can significantly increase the total amount of active ingredient ferulic acid, and significantly improve the therapeutic effect of Tongbianling capsules.

[0032] (2) The present inventor found that during extraction, adding a specific composite enzyme can efficiently extract active ingredients sennoside B from senna leaves, active ingredient ferulic acid from angelica, and active ingredient echinacoside from cistanche, reduce the extraction temperature, and avoid decomposition of active ingredients at high temperature. The Tongbianling capsules prepared by the present application have a content of sennoside B of 10 mg / g, a content of ferulic acid of 1.4 mg / g, and a content of echinacoside of more than 7 mg / g.

[0033] (3) Pretreatment of talc with a specific method can improve the stability of active ingredients, and after 6 months of storage, the stability is good. DETAILED DESCRIPTION

[0034] The present application discloses a Tongbianling capsule and a preparation method thereof. Those skilled in the art can refer to the content of the present application, combine the relevant principles of pharmaceutical preparations, and appropriately improve the process parameters to realize it. It should be particularly pointed out that all similar substitutions and changes are obvious to those skilled in the art, and they are considered to be included in the scope of the present application. The application of the present application has been described by the preferred embodiments, and the relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present application to realize and apply the present application technology.

[0035] In order to better understand the present application without limiting the scope of the present application, all numbers, percentages and other numerical values used in this application should be understood as being modified by the word "about" in all cases. Each numerical parameter should be considered at least as obtained by the conventional rounding method.

[0036] The present application is further illustrated by the following examples, but the examples do not limit the present application in any way.

[0037] Dose difference: according to the method of dose difference in Chinese Pharmacopoeia 2020 edition part three 0104 granules, the dose difference was determined.

[0038] Examples 1-4: Tongbianling capsules

[0039] I. Prescription composition:

[0040] According to the prescription amount of 20000 particles, Tongbianling capsules were prepared, and the same was used.

[0041]

[0042]

[0043] II. Preparation method:

[0044] (1) Preparation of Angelica sinensis powder

[0045] ① Cleaning and pretreatment: Angelica sinensis was washed with water 2-3 times, and the amount of water was 2-3 times the weight of Angelica sinensis; after cleaning, it was added to 2.0% potassium permanganate solution, and the weight of potassium permanganate solution was 3 times the weight of Angelica sinensis, the temperature was controlled at 0-5℃, and the stirring time was 1.5h; the temperature was increased to 10-15℃, and the stirring time was 3h.

[0046] ② Drying: drying under reduced pressure until the moisture content is less than 8.0%.

[0047] ③ Grinding: take 50% of the dried Angelica sinensis, grind, and the D90, D50 are as follows:

[0048] Example D90 (pm) D50 (pm) Example 1 93.1 71.8 Example 2 96.9 73.5 Example 3 105.1 83.3 Example 4 94.7 69.8

[0049] (2) Preparation of extract powder

[0050] ① The remaining Angelica sinensis, Psyllium leaf and Cistanche were added with 10-12 times the amount of water, and a composite enzyme composed of cellulase, pectinase and ligninase was added, the pH was adjusted to 4.5-5.5, and the extraction was carried out at 50-55℃ for 5h, then filtered and concentrated into thick paste.

[0051] The weight ratio of cellulase, pectinase and ligninase in the composite enzyme is 1:0.8:0.5; the weight ratio of the composite enzyme to Psyllium leaf is 0.2:24.

[0052] ② Drying and grinding: the extract was dried under reduced pressure, ground, and the D90, D50 were as follows:

[0053] Example D90 (pm) D50 (pm) Example 1 79.1 57.9 Example 2 85.8 65.1 Example 3 92.2 69.8 Example 4 80.4 59.6

[0054] (3) Preparation of capsules

[0055] ① Pretreatment of talc powder: add 25% of the total amount of talc powder into the talc powder citric acid buffer solution (pH 5.5), ball mill in a ball mill for 2h, after ball milling, wash with water, dry, and then heat activate at 90-100℃ for 30min, and then cool to room temperature.

[0056] ②Mix angelica powder, extract powder, talc powder and corn starch for 10min, and load into the capsule shell. Each capsule contains 0.25g.

[0057] III. Test results:

[0058] (1) Loading difference: as shown in the following table

[0059] Example Dose difference (Internal control: within ±8%) Conclusion Example 1 -3.32％～4.79％ Complied with the requirements Example 2 -4.83％～2.87％ Complied with the requirements Example 3 -3.39％～3.24％ Complied with the requirements Example 4 -5.44％～3.25％ Complied with the requirements

[0060] (2) The content of active ingredient sennoside B in senna leaves, active ingredient ferulic acid in angelica, and active ingredient echinacoside in cistanche

[0061] Example Sennoside B (mg / g) Olibanic acid (mg / g) Syringin (mg / g) Example 1 10.94 1.55 7.23 Example 2 10.24 1.43 7.02 Example 3 10.41 1.46 7.34 Example 4 10.66 1.59 7.32

[0062] The prepared laxative capsule has a loading difference meeting the requirements.

[0063] The laxative capsule prepared by the present application has a content of sennoside B of more than 10mg / g, a content of ferulic acid of more than 1.4mg / g, and a content of echinacoside of more than 7mg / g, which ensures the therapeutic effect of the laxative capsule. The therapeutic effect is significantly better than that of commercially available preparations.

[0064] Comparative Example 1: laxative capsule

[0065] I. Prescription composition: same as Example 1.

[0066] II. Preparation method:

[0067] (1) Preparation of angelica powder

[0068] ① Washing: wash the angelica with clean water for 2-3 times, and the amount of water is 2-3 times of the weight of the angelica;

[0069] ② Drying: dry under reduced pressure until the moisture content is less than 8.0%.

[0070] ③ Grinding: take 50% of the dried angelica, grind, and the D90 and D50 are as follows:

[0071] Comparative example D90 (pm) D50 (pm) Comparative example 1 99.5 86.6

[0072] (2) Preparation of extract powder

[0073] ①Residual angelica, senna leaf, cistanche, 10-12 times the amount of water, decoction 1.5 hours, filter, filter concentrate into thick paste.

[0074] ②Dry, powder: the extract was dried under reduced pressure, powder, D90, D50 as follows:

[0075] Comparative example D90 (pm) D50 (pm) Comparative example 1 85.8 73.7

[0076] (3) Preparation of capsules

[0077] Angelica powder, extract powder, talc, corn starch mixed for 10 min, loaded into the capsule shell. Each 0.25 g.

[0078] III. Test results:

[0079] (1) Loading differences: as shown in the table below

[0080] Comparative example Dose difference (Internal control: within ±4%) Conclusion Comparative example 1 -5.84％～3.09％ Complied with the requirements

[0081] (2) Active ingredient sennoside B in senna leaf, active ingredient ferulic acid in angelica, active ingredient echinacoside in cistanche

[0082] Comparative example Sennoside B (mg / g) Olibanic acid (mg / g) Syringin (mg / g) Comparative example 1 5.02 0.48 2.88

[0083] Comparative Example 1 was prepared by the pharmacopoeia method to obtain the laxative capsule, the content of sennoside B was only 5.02 mg / g, the content of ferulic acid was only 0.48 mg / g or more, and the content of echinacoside was only 2.88 mg / g, which was significantly worse than Examples 1-4. The test showed that the effect of treating constipation was significantly worse than Examples 1-4.

[0084] Comparative Examples 2-6: Effect of pretreatment during angelica powder preparation on laxative capsules

[0085] I. Prescription composition: same as Example 1

[0086] II. Preparation method: the "① cleaning, pretreatment" step in step (1) is shown in the table below, and the remaining steps are the same as Example 1.

[0087]

[0088]

[0089] III. Test results:

[0090] (1) Loading differences: as shown in the table below

[0091] Comparative example Dose difference (Internal control: within ±4%) Conclusion Comparative example 2 -4.07％～2.80％ Complied with the requirements Comparative example 3 -3.21％～2.85％ Complied with the requirements Comparative example 4 -4.80％～3.13％ Complied with the requirements Comparative example 5 -3.58％～3.21％ Complied with the requirements

[0092] (2) The content of active ingredient sennoside B in senna leaf, active ingredient ferulic acid in angelica, and active ingredient echinacoside in cistanche

[0093] Comparative example Sennoside B (mg / g) Olibanic acid (mg / g) Syringin (mg / g) Comparative example 2 10.64 0.52 6.61 Comparative example 3 10.21 1.14 6.75 Comparative example 4 10.17 1.19 6.96 Comparative example 5 10.45 1.25 6.83

[0094] Comparative Examples 2-5 differ from Example 1 only in the different soaking process of angelica, and the content of active ingredient ferulic acid is significantly different from Example 1. After testing, the effect of treating constipation is significantly different from Example 1.

[0095] In combination with the detection results of active ingredients in Examples 1-4 and Comparative Examples 2-5, angelica is soaked and pretreated, preferably 2.0% potassium permanganate solution, more preferably the temperature is controlled at 0-5℃, and stirring is performed for 1-2h; the temperature is raised to 10-15℃, and stirring is performed for 2-4h. The content of ferulic acid in the prepared laxative capsule is significantly increased to 1.4mg / g or more.

[0096] Comparative Examples 6-10: Effect of adding complex enzymes during the preparation of extract powder on laxative capsules

[0097] I. Prescription composition: the prescriptions of Comparative Examples 6-10 are the same as Example 1.

[0098] II. Preparation method: the "①" step in step (2) is shown in the following table, and the remaining steps are the same as Example 1.

[0099]

[0100]

[0101] III. Detection results:

[0102] (1) Weight difference: as shown in the following table

[0103] Comparative example Dose difference (Internal control: within ±8%) Conclusion Comparative example 6 -3.92％～3.46％ Complied with the requirements Comparative example 7 -3.34％～3.03％ Complied with the requirements Comparative example 8 -3.73％～2.58％ Complied with the requirements Comparative example 9 -4.22％～5.56％ Complied with the requirements Comparative example 10 -4.01％～4.45％ Complied with the requirements

[0104] (2) The content of active ingredient sennoside B in senna leaf, active ingredient ferulic acid in angelica, and active ingredient echinacoside in cistanche

[0105]

[0106]

[0107] Comparative Examples 6-10 differ from Example 1 only in whether complex enzymes are used during extraction. The content of active ingredients in Comparative Examples 6-10 is significantly different from Example 1. After testing, the effect of treating constipation is significantly different from Example 1.

[0108] In combination with the detection results of the active ingredients in Examples 1-4 and Comparative Examples 6-10, during extraction, the complex enzyme with a weight ratio of cellulase, pectinase and ligninase of 1:0.8:0.5 is preferably added; the weight ratio of the complex enzyme to senna is 0.2:24, and the prepared Purgative Capsule is obtained.

[0109] Comparative Examples 11-13: Purgative Capsule

[0110] I. Prescription composition: same as Example 1

[0111] II. Preparation method: the "③ powdering" in step (1) and the "② drying and powdering" in step (2) are as shown in the following table, and the remaining steps are the same as Example 1.

[0112]

[0113] III. Detection results:

[0114] (1) Loading difference: as shown in the following table

[0115]

[0116]

[0117] (2) The contents of active ingredients sennoside B in senna, ferulic acid in angelica and echinacoside in cistanche

[0118] Since the loading difference does not meet the requirements, the contents of active ingredients are not detected.

[0119] According to the test results of Comparative Examples 11-13, the particle size of angelica powder and the particle size of extract powder affect the loading difference.

[0120] Therefore, in combination with the loading difference results of Examples 1-4 and Comparative Examples 11-13, it is preferred that the D90 of angelica powder is not more than 120 μm, the D50 is not more than 100 μm, the D90 of extract powder is not more than 110 μm, and the D50 is not more than 90 μm, and the prepared Purgative Capsule meets the requirements of loading difference.

[0121] Comparative Example 14: Purgative Capsule

[0122] I. Prescription composition: same as Example 1

[0123] II. Preparation method: the talc powder is not pretreated, i.e. there is no step of "① pretreatment of talc powder" in step (3).

[0124] III. Detection results:

[0125] (1) Loading difference: as shown in the following table

[0126] Comparative example Dose difference (Internal control: within ±8%) Conclusion Comparative example 14 -5.11％～4.42％ Complied with the requirements

[0127] (2) the content of active ingredient sennoside B in senna leaf, active ingredient ferulic acid in angelica, and active ingredient echinacoside in cistanche

[0128] Comparative example Sennoside B (mg / g) Olibanic acid (mg / g) Syringin (mg / g) Comparative example 14 10.53 1.57 7.12

[0129] Example 5: Accelerated test

[0130] The laxative capsules prepared in Examples 1-4 and Comparative Example 14 were placed under accelerated conditions for 6 months, and the content of active ingredients was detected.

[0131] Example Sennoside B (mg / g) Olibanic acid (mg / g) Syringin (mg / g) Example 1 10.88 1.52 7.13 Example 2 10.24 1.41 7.01 Example 3 10.27 1.42 7.21 Example 4 10.56 1.53 7.22 Comparative example 14 Comparative example 14 9.49 1.34 6.58

[0132] The content of sennoside B in the laxative capsules prepared in the present application can still reach more than 10 mg / g, the content of ferulic acid can still reach more than 1.4 mg / g, and the content of echinacoside can still reach more than 7 mg / g after being placed under accelerated conditions for 6 months. The content of active ingredients in the laxative capsules prepared in Examples 1-4 of the present application does not change significantly after being placed under accelerated conditions for 6 months, and the stability is good, thereby ensuring the therapeutic effect of the laxative capsules.

[0133] The content of active ingredients in the laxative capsules prepared in Comparative Example 14 of the present application decreased significantly after being placed under accelerated conditions for 6 months, and the quality is unstable.

Claims

1. A laxative capsule, prepared from the following components in parts by weight: ； The preparation method of the laxative capsule comprises the following steps: (1) Preparation of Angelica sinensis powder ① Washing and pretreatment: Wash Angelica sinensis with water for 2-3 times, with the amount of water being 2-3 times the weight of Angelica sinensis each time. After washing, add 1.8%-2.2% potassium permanganate solution, with the weight of potassium permanganate solution being 2-4 times the weight of Angelica sinensis, control the temperature at 0-5℃, and stir for 1-2 hours. Then, increase the temperature to 10-15℃, and stir for 2-4 hours. ② Drying: Dry under reduced pressure until the moisture content is less than 8.0%. ③ Grinding: Take 50% of the dried Angelica sinensis, grind it, and the D90 is not more than 120μm, and the D50 is not more than 100μm. (2) Preparation of extract powder ① Add 10-12 times the amount of water to the remaining Angelica sinensis, senna leaf, and desert ginseng, and add a composite enzyme composed of cellulase, pectinase, and ligninase. Adjust the pH to 4.5-5.5, extract at 50℃-55℃ for 4-6 hours, filter, and concentrate the filtrate into a thick extract. The weight ratio of cellulase, pectinase, and ligninase in the composite enzyme is 1:0.8:0.5, and the weight ratio of the composite enzyme to senna leaf is 0.1-0.3:

24. ② Drying and grinding: Dry the extract under reduced pressure, and grind it, with the D90 being not more than 110μm, and the D50 being not more than 90μm. (3) Preparation of the capsule ① Pretreatment of talc powder: Add 20-30% of the total amount of talc powder to the talc powder in a pH 5.5 citrate buffer solution, and ball mill in a ball mill for 1-2 hours. After ball milling, wash with water, dry, and then heat activate at 90-100℃ for 30 minutes, and then cool to room temperature. ② Mix the Angelica sinensis powder, extract powder, talc powder, and corn starch for 10 minutes, and load into the capsule shell.

2. The Senexon capsule as set forth in claim 1, wherein prepared from the following components: 。 3. The Senexon capsule as set forth in claim 2, wherein prepared from the following components: 。 4.A method for preparing any one of the laxative capsules of claims 1-3, comprising the following steps: (1) Preparation of Angelica sinensis powder ① Washing and pretreatment: Wash Angelica sinensis with water for 2-3 times, with the amount of water being 2-3 times the weight of Angelica sinensis each time. After washing, add 1.8%-2.2% potassium permanganate solution, with the weight of potassium permanganate solution being 2-4 times the weight of Angelica sinensis, control the temperature at 0-5℃, and stir for 1-2 hours. Then, increase the temperature to 10-15℃, and stir for 2-4 hours. ② Drying: Dry under reduced pressure until the moisture content is less than 8.0%. ③ Grinding: Take 50% of the dried Angelica sinensis, grind it, and the D90 is not more than 120μm, and the D50 is not more than 100μm. (2) Preparation of extract powder ① Add 10-12 times the amount of water to the remaining Angelica sinensis, senna leaf, and desert ginseng, and add a composite enzyme composed of cellulase, pectinase, and ligninase. Adjust the pH to 4.5-5.5, extract at 50℃-55℃ for 4-6 hours, filter, and concentrate the filtrate into a thick extract. The weight ratio of cellulase, pectinase, and ligninase in the composite enzyme is 1:0.8:0.5, and the weight ratio of the composite enzyme to senna leaf is 0.1-0.3:

24. ②Drying and powdering: drying the extract under reduced pressure, powdering, D90 not more than 110 μm, D50 not more than 90 μm; (3) Preparation of the capsule ①Pre-treatment of the talc powder: adding 20-30% of the total amount of talc powder into pH 5.5 citrate buffer solution, ball milling in a ball mill for 1-2 h, washing with water and drying after the ball milling, and then heating and activating at 90-100 ℃ for 30 min, and then cooling to room temperature; ②Mixing angelica powder, extract powder, talc powder and corn starch for 10 min, and loading into the capsule shell.

5. The production method according to claim 4, wherein In step (1), the potassium permanganate solution is 2.0%.

6. The production method according to claim 4, wherein In step (1), the weight of the potassium permanganate solution is 3 times the weight of the angelica.

7. The production method according to claim 4, wherein In step (2), the weight ratio of the complex enzyme to senna is 0.2:

24.

8. The production method according to claim 4, wherein In step (3), the citric acid buffer solution is 25%.

9. The Senexon capsule as set forth in claim 1, wherein Each capsule contains 0.25 g of content.

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