A pharmaceutical composition for treating constipation, and a preparation method and use thereof

Abstract

The present application relates to a kind of pharmaceutical composition for treating constipation and its preparation method and use, and the pharmaceutical composition is made of senna 80%, angelica 10%, cistanche 10%.In the present application, cistanche is treated by using extraction, adsorption and other extraction methods, to reduce the content of metal toxic substances, and avoid the poisoning reaction that appears in long-term use.

Description

Technical Field

[0001] This invention belongs to the field of Tibetan medicine technology, and specifically relates to a pharmaceutical composition for treating constipation, its preparation method, and its uses. Background Technology

[0002] Tongbianling Capsules are used to clear heat, promote bowel movement, and relieve constipation. They are indicated for constipation due to heat accumulation, constipation due to prolonged bed rest, temporary abdominal distension and constipation, and habitual constipation in the elderly. Its ingredients are senna leaf, angelica root, and cistanche.

[0003] Currently, the main problem with the production of laxative capsules by enterprises is the excessive metal content of its core raw material, Cistanche deserticola, which manifests in the following aspects:

[0004] 1. The lead content in Cistanche deserticola exceeded the standard in 17.2% of the samples, with a lead content range of 5-30 mg / kg.

[0005] 2. The arsenic content in Cistanche deserticola exceeded the standard in 14.6% of the samples, with the arsenic content ranging from 2 to 7 mg / kg.

[0006] 3. The cadmium content in Cistanche deserticola exceeded the standard in 19.6% of the samples, with a cadmium content range of 1-5 mg / kg.

[0007] 4. The mercury content in Cistanche deserticola exceeded the standard in 8.9% of the samples, with the mercury content ranging from 0.2 to 1.1 mg / kg.

[0008] 5. The copper content in Cistanche deserticola exceeded the standard in 14.8% of the samples, with a copper content range of 10-105 mg / kg.

[0009] 6. The zinc content in Cistanche deserticola exceeded the standard in 18.7% of the samples, with a zinc content range of 5-40 mg / kg.

[0010] Modern medicine has proven that excessive metals have a significant harmful effect on human metabolism and normal physiological functions. High levels of metals in the body can lead to various diseases. For example, lead poisoning can directly damage the thyroid function of humans and animals; the typical symptom of cadmium poisoning is kidney damage; excessive copper can denature hemoglobin, inhibit the activity of some enzymes, and also lead to cardiovascular diseases; mercury poisoning severely affects the central nervous system; the toxicity of arsenic compounds mainly involves binding to the sulfhydryl groups of enzyme systems, causing enzyme dysfunction and affecting normal cell metabolism; zinc poisoning easily causes nausea, diarrhea, fever, chills, and in severe cases, can lead to high blood pressure, shortness of breath, and shock.

[0011] The main methods disclosed domestically for removing heavy metals from traditional Chinese medicine extracts include flocculation precipitation, macroporous chelating resin method, supercritical CO2 extraction, γ-mercaptopropyl-bonded silica gel method, and others. The main problems are:

[0012] 1. Flocculation and sedimentation is simple and quick to operate and does not pollute the environment, but its removal efficiency is not high.

[0013] 2. The macroporous chelating resin method uses simple equipment and has a good adsorption effect, but the adsorption effect is easily affected, the operation is complicated, and the process technology requirements are high.

[0014] 3. Supercritical CO2 complexation extraction has high sensitivity and accuracy, good selectivity, no secondary solvent pollution, good repeatability, and low loss of effective components. However, it is not easy to select suitable complexing agents, and the equipment is expensive, resulting in high production costs.

[0015] 4. The γ-mercaptopropyl bonded silica gel method has a good removal effect and less loss of effective components of traditional Chinese medicine, but the cost is relatively high.

[0016] 5. The above methods have a good effect on removing metal ions, but the range of heavy metal elements that can be applied is limited. They can only reduce the content of one or two metal ions, and cannot simultaneously meet the requirement of reducing the content of six metal ions. Summary of the Invention

[0017] This invention aims to solve the technical problems existing in the prior art. To this end, this invention proposes a laxative capsule pharmaceutical composition, its preparation method, and its uses. By employing extraction methods such as soaking and adsorption, the content of metal ions is reduced, thus avoiding the toxic reactions that may occur with long-term use of laxative capsules.

[0018] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0019] The first aspect of the present invention relates to a pharmaceutical composition for treating constipation, which is made from the following raw materials in parts by weight: 80% senna leaves, 10% angelica sinensis, and 10% cistanche deserticola;

[0020] The Cistanche deserticola mentioned above:

[0021] Lead content: <2 mg / kg;

[0022] Arsenic content: <0.4 mg / kg;

[0023] Cadmium content: <0.4 mg / kg;

[0024] Mercury content: <0.09 mg / kg;

[0025] Copper content: <10mg / kg;

[0026] Zinc content: <5mg / kg.

[0027] The present invention also provides a method for preparing the above-mentioned pharmaceutical composition, comprising the following steps:

[0028] (1) Grinding and sieving

[0029] First, senna leaves, cistanche and angelica are sieved to remove visible foreign matter, and then crushed and sieved.

[0030] (2) Processing of Cistanche deserticola

[0031] After crushing and sieving, the Cistanche deserticola was extracted and then separated into solid A and liquid B.

[0032] Liquid B is adsorbed and then collected.

[0033] (3) Preparation of dry paste

[0034] Solid A and senna leaves are added to liquid B and stirred for 80-120 minutes; then decocted for 20-30 minutes; after filtration, the filtrate is concentrated to obtain a dry extract.

[0035] (4) Grinding, sieving, and preparing capsules

[0036] The dried extract was pulverized, mixed with Angelica sinensis, and sieved. Empty capsules and capsule filling equipment were used to obtain laxative capsules.

[0037] The crushing and sieving mentioned in step (1) refers to: using a crusher to crush each raw material and passing it through a 200-mesh sieve.

[0038] In step (2),

[0039] The extraction process involves adding Cistanche deserticola to purified water, heating the mixture to 60-80℃, adding tartaric acid, adjusting the pH to 2-3, stirring for 80-120 minutes, adding sodium hydroxide, adjusting the pH to 9-10, stirring for another 80-120 minutes, and then filtering to separate the solid and liquid components.

[0040] Purified water dosage: WCistanche : Lpurified water = 1 kg : 2-3 L;

[0041] The adsorption refers to: adding an adsorbent to the chromatography column at an adsorption rate of 5 Bv / h; eluting with purified water at a rate of 3 Bv / h during the elution process, and collecting the water eluent.

[0042] Adsorbent dosage: WCistanche : Wadsorbent = 1 kg : 0.4-0.8 kg;

[0043] The height-to-diameter ratio of the chromatography column is 8-10:1;

[0044] The adsorbent refers to:

[0045] (1) Crush the jujube pits and plum shells (without kernels) separately, pass them through a 200-mesh sieve and mix them. Add 10-15% hydrochloric acid solution to adjust the pH to 2.5-3 and stir for 30-50 min; add 20-25% sodium hydroxide to adjust the pH to 9.5-10 and stir for 30-50 min, then filter, separate the solid and liquid, and dry to obtain the mixture.

[0046] (2) Adjust the pH of purified water to 2.8-3.2, add the mixture and 4-methoxybenzamide respectively, heat to 60-80℃, add anhydrous aluminum trichloride, and continue stirring for 100-120 min; after cooling to room temperature, filter, wash the wet solid twice with purified water and then dry.

[0047] Purified water usage: Wmixture : Lpurified water = 1 kg : 4-8 L;

[0048] Dosage of 4-methoxybenzamide: W mixture : W4-methoxybenzamide = 1 kg : 1.2-1.6 kg;

[0049] Anhydrous aluminum trichloride dosage: Wmixture : Wanhydrous aluminum trichloride = 1 kg : 6-10 g;

[0050] The amount of purified water used in the washing process is: Wmixture : Lpurified water = 1 kg : 11-15 L;

[0051] (3) After drying, the solid is crushed and sieved, sodium bentonite is added, and after stirring evenly, purified water is added and stirring is continued to make a soft material, which is then passed through a 150-mesh sieve and placed in a crucible.

[0052] Sodium-based bentonite dosage: Wmixture : Wsodium-based bentonite = 1 kg : 60-80 g;

[0053] Purified water dosage: W mixture : L purified water = 1 kg : 80-100 ml;

[0054] (4) Place the crucible in a muffle furnace and heat it from room temperature to 220-240℃ at a rate of 20℃ / min for 40-60 min for carbonization. Remove the crucible, allow it to cool naturally to room temperature, and pass it through a 150-mesh sieve to obtain the composite adsorbent.

[0055] In step (3), the amount of purified water used is: WCistanche:Lpurified water = 1kg:3-5L; the decoction refers to controlling the temperature at 90-100℃ and the time at 60-80min. The number of decoctions is 2-3 times.

[0056] The present invention also provides the use of the above-described pharmaceutical composition or the pharmaceutical composition prepared by the above-described preparation method in the preparation of a medicine for treating constipation.

[0057] The technical advantages of this invention are:

[0058] 1. Effectively reduces metal ion content

[0059] Domestic literature reports methods for removing metal ions. Technicians applied these methods to the study of metal ion removal from Cistanche deserticola, conducted three consecutive experiments, and collected experimental data. The specific results are shown in the table below.

[0060] Summary table of metal ion removal rates

[0061]

[0062]

[0063] The removal rate of metal ions from Cistanche deserticola using the method described in this invention is shown in the table below.

[0064] Summary table of metal ion removal rates

[0065]

[0066] Analysis suggests that the method described in this invention can effectively remove metal ions, and its technical effect is significantly better than existing technologies and processes.

[0067] 2. The effective components of Cistanche deserticola have not been reduced.

[0068] Studies have found that applying domestically published metal ion removal methods to Cistanche deserticola also reduces the content of its active ingredients. For example, methods such as flocculation precipitation and resin adsorption can lower the effective content, affecting product quality. Using the method described in this invention, the decrease in effective content is controlled within 5%, and the product quality meets the Chinese Pharmacopoeia's requirements for Cistanche deserticola.

[0069] 3. Avoid poisoning reactions

[0070] Producing laxative capsules according to the method described in this invention can effectively avoid poisoning reactions caused by metal ions. Specific implementation methods

[0071] The invention is illustrated below with examples. It should be understood that these examples are for illustrative purposes only and not for limiting the invention. The scope and core content of the invention are defined by the claims.

[0072] Determination of Cistanche deserticola content: The content was determined by high performance liquid chromatography as described in the quality standard of Cistanche deserticola in the 2020 edition of the Chinese Pharmacopoeia.

[0073] Example 1

[0074] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0075] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0076] Lead content: 6.4 mg / kg;

[0077] Arsenic content: 3.6 mg / kg;

[0078] Cadmium content: 4.8 mg / kg;

[0079] Mercury content: 0.9 mg / kg;

[0080] Copper content: 48.4 mg / kg;

[0081] Zinc content: 36.7 mg / kg;

[0082] (1) Grinding and sieving

[0083] First, senna leaves, cistanche and angelica are screened to remove visible foreign matter, and then crushed and passed through a 200-sieve.

[0084] (2) Processing of Cistanche deserticola

[0085] The pulverized and sieved Cistanche deserticola was added to 20 L of purified water, heated to 60 °C, and tartaric acid was added to adjust the pH to 2. The mixture was stirred for 80 min. After stirring, sodium hydroxide was added to adjust the pH to 9, and the mixture was stirred for another 80 min. The mixture was then filtered to separate the solid and liquid components. After solid-liquid separation, 19.8 L of wet solid A and liquid B were obtained.

[0086] 4 kg of adsorbent was added to the chromatography column, with an adsorption rate of 5 Bv / h. During elution, purified water was used at a rate of 3 Bv / h, and 46.3 L of eluent was collected. The results were analyzed and calculated as follows:

[0087] Lead content: 0.49 mg / kg;

[0088] Arsenic content: 0.21 mg / kg;

[0089] Cadmium content: 0.41 mg / kg;

[0090] Mercury content: 0.07 mg / kg;

[0091] Copper content: 0.9 mg / kg;

[0092] Zinc content: 4.59 mg / kg;

[0093] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O 20 ) and verbascoside (C 29 H 36 O15 The total is 0.42%.

[0094] (3) Preparation of dry paste

[0095] Solid A and senna leaves were added to the water wash solution and stirred for 80 minutes; then decocted for 20 minutes; the filtrate was concentrated after filtration to obtain 12.5 kg of dry extract.

[0096] (4) Grinding, sieving, and preparing capsules

[0097] The dried extract was pulverized, mixed with Angelica sinensis, and sieved. Empty capsules and capsule filling equipment were used to obtain laxative capsules.

[0098] Example 2

[0099] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0100] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0101] Lead content: 10.7 mg / kg;

[0102] Arsenic content: 6.5 mg / kg;

[0103] Cadmium content: 4.2 mg / kg;

[0104] Mercury content: 1.0 mg / kg;

[0105] Copper content: 67.3 mg / kg;

[0106] Zinc content: 35.1 mg / kg;

[0107] (1) Grinding and sieving

[0108] First, senna leaves, cistanche and angelica are screened to remove visible foreign matter, and then crushed and passed through a 200-sieve.

[0109] (2) Processing of Cistanche deserticola

[0110] The pulverized and sieved Cistanche deserticola was added to 22 L of purified water, heated to 65 °C, and tartaric acid was added to adjust the pH to 2.3. The mixture was stirred for 90 min. After stirring, sodium hydroxide was added to adjust the pH to 9.2, and the mixture was stirred for another 90 min. The mixture was then filtered to separate the solid and liquid components. After solid-liquid separation, 21.9 L of wet solid A and liquid B were obtained.

[0111] 5 kg of adsorbent was added to the chromatography column, with an adsorption rate of 5 Bv / h. During elution, purified water was used at a rate of 3 Bv / h, and 50.7 L of eluent was collected. The results were analyzed and calculated as follows:

[0112] Lead content: 0.80 mg / kg;

[0113] Arsenic content: 0.36 mg / kg;

[0114] Cadmium content: 0.35 mg / kg;

[0115] Mercury content: 0.079 mg / kg;

[0116] Copper content: 6.32 mg / kg;

[0117] Zinc content: 4.39 mg / kg;

[0118] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O 20 ) and verbascoside (C 29 H 36 O 15 The total is 0.46%.

[0119] (3) Preparation of dry paste

[0120] Solid A and senna leaves were added to the water wash solution and stirred for 85 minutes; then decocted for 22 minutes; the filtrate was concentrated after filtration to obtain 12.6 kg of dry extract.

[0121] (4) Grinding, sieving, and preparing capsules

[0122] The dried extract was pulverized, mixed with Angelica sinensis, and sieved. Empty capsules and capsule filling equipment were used to obtain laxative capsules.

[0123] Example 3

[0124] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0125] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0126] Lead content: 26.4 mg / kg;

[0127] Arsenic content: 1.8 mg / kg;

[0128] Cadmium content: 1.6 mg / kg;

[0129] Mercury content: 0.21 mg / kg;

[0130] Copper content: 17.5 mg / kg;

[0131] Zinc content: 5.21 mg / kg;

[0132] (1) Grinding and sieving

[0133] First, senna leaves, cistanche and angelica are screened to remove visible foreign matter, and then crushed and passed through a 200-sieve.

[0134] (2) Processing of Cistanche deserticola

[0135] The pulverized and sieved Cistanche deserticola was added to 25 L of purified water, heated to 70 °C, and tartaric acid was added to adjust the pH to 2.5. The mixture was stirred for 100 min. After stirring, sodium hydroxide was added to adjust the pH to 9.5, and the mixture was stirred for 100 min. Then, the mixture was filtered to separate the solid and liquid components. After solid-liquid separation, 24.9 L of wet solid A and liquid B were obtained.

[0136] 6 g of adsorbent was added to the chromatography column, with an adsorption rate of 5 Bv / h. During elution, purified water was used at a rate of 3 Bv / h, and 57.6 L of eluent was collected. The results were analyzed and calculated as follows:

[0137] Lead content: 2.0 mg / kg;

[0138] Arsenic content: 0.10 mg / kg;

[0139] Cadmium content: 0.13 mg / kg;

[0140] Mercury content: 0.016 mg / kg;

[0141] Copper content: 1.66 mg / kg;

[0142] Zinc content: 0.65 mg / kg;

[0143] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O 20 ) and verbascoside (C 29 H 36 O 15 The total is 0.43%.

[0144] (3) Preparation of dry paste

[0145] Solid A and senna leaves were added to the water wash solution and stirred for 90 minutes; then decocted for 25 minutes; the filtrate was concentrated after filtration to obtain 12.6 kg of dry extract.

[0146] (4) Grinding, sieving, and preparing capsules

[0147] The dried extract was pulverized, mixed with Angelica sinensis, and sieved. Empty capsules and capsule filling equipment were used to obtain laxative capsules.

[0148] Example 4

[0149] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0150] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0151] Lead content: 4.2 mg / kg;

[0152] Arsenic content: 1.5 mg / kg;

[0153] Cadmium content: 2.3 mg / kg;

[0154] Mercury content: 0.36 mg / kg;

[0155] Copper content: 24.3 mg / kg;

[0156] Zinc content: 9.7 mg / kg;

[0157] (1) Grinding and sieving

[0158] First, senna leaves, cistanche and angelica are screened to remove visible foreign matter, and then crushed and passed through a 200-sieve.

[0159] (2) Processing of Cistanche deserticola

[0160] The pulverized and sieved Cistanche deserticola was added to 27 L of purified water, heated to 75 °C, and tartaric acid was added to adjust the pH to 2.7. The mixture was stirred for 110 min. After stirring, sodium hydroxide was added to adjust the pH to 9.8, and the mixture was stirred for 110 min. Then, the mixture was filtered to separate the solid and liquid components. After solid-liquid separation, 26.9 L of wet solid A and liquid B were obtained.

[0161] 7 kg of adsorbent was added to the chromatography column, with an adsorption rate of 5 Bv / h. During elution, purified water was used at a rate of 3 Bv / h, and 64.5 L of eluent was collected. The results were analyzed and calculated as follows:

[0162] Lead content: 0.32 mg / kg;

[0163] Arsenic content: 0.086 mg / kg;

[0164] Cadmium content: 0.19 mg / kg;

[0165] Mercury content: 0.03 mg / kg;

[0166] Copper content: 2.31 mg / kg;

[0167] Zinc content: 1.20 mg / kg;

[0168] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O 20 ) and verbascoside (C29 H 36 O 15 The total is 0.39%.

[0169] (3) Preparation of dry paste

[0170] Solid A and senna leaves were added to the water wash solution and stirred for 95 minutes; then decocted for 28 minutes; the filtrate was concentrated after filtration to obtain 12.8 kg of dry extract.

[0171] (4) Grinding, sieving, and preparing capsules

[0172] The dried extract was pulverized, mixed with Angelica sinensis, and sieved. Empty capsules and capsule filling equipment were used to obtain laxative capsules.

[0173] Example 5

[0174] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0175] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0176] Lead content: 3.8 mg / kg;

[0177] Arsenic content: 2.6 mg / kg;

[0178] Cadmium content: 0.74 mg / kg;

[0179] Mercury content: 0.18 mg / kg;

[0180] Copper content: 20.3 mg / kg;

[0181] Zinc content: 30.4 mg / kg;

[0182] (1) Grinding and sieving

[0183] First, senna leaves, cistanche and angelica are screened to remove visible foreign matter, and then crushed and passed through a 200-sieve.

[0184] (2) Processing of Cistanche deserticola

[0185] The pulverized and sieved Cistanche deserticola was added to 30L of purified water, heated to 80℃, and tartaric acid was added to adjust the pH to 3.0. The mixture was stirred for 120 minutes. After stirring, sodium hydroxide was added to adjust the pH to 10.0, and the mixture was stirred for another 120 minutes. The mixture was then filtered to separate the solid and liquid phases. After solid-liquid separation, 29.8L of wet solid A and liquid B were obtained.

[0186] 8 kg of adsorbent was added to the chromatography column, with an adsorption rate of 5 Bv / h. During elution, purified water was used at a rate of 3 Bv / h, and 64.5 L of eluent was collected. The results were analyzed and calculated as follows:

[0187] Lead content: 0.28 mg / kg;

[0188] Arsenic content: 0.14 mg / kg;

[0189] Cadmium content: 0.06 mg / kg;

[0190] Mercury content: 0.014 mg / kg;

[0191] Copper content: 1.91 mg / kg;

[0192] Zinc content: 3.74 mg / kg;

[0193] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O 20 ) and verbascoside (C 29 H 36 O 15 The total is 0.41%.

[0194] (3) Preparation of dry paste

[0195] Solid A and senna leaves were added to the water wash solution and stirred for 100 minutes; then decocted for 30 minutes; the filtrate was concentrated after filtration to obtain 12.9 kg of dry extract.

[0196] (4) Grinding, sieving, and preparing capsules

[0197] The dried extract was pulverized, mixed with Angelica sinensis, and sieved. Empty capsules and capsule filling equipment were used to obtain laxative capsules.

[0198] Example 6

[0199] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0200] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0201] Lead content: 3.7 mg / kg;

[0202] Arsenic content: 2.8 mg / kg;

[0203] Cadmium content: 3.6 mg / kg;

[0204] Mercury content: 0.76 mg / kg;

[0205] Copper content: 17.5 mg / kg;

[0206] Zinc content: 32.1 mg / kg;

[0207] (1) Grinding and sieving

[0208] First, senna leaves, cistanche and angelica are screened to remove visible foreign matter, and then crushed and passed through a 200-sieve.

[0209] (2) Processing of Cistanche deserticola

[0210] The pulverized and sieved Cistanche deserticola was added to 25 L of purified water, heated to 75 °C, and tartaric acid was added to adjust the pH to 2.6. The mixture was stirred for 100 min. After stirring, sodium hydroxide was added to adjust the pH to 9.4, and the mixture was stirred for 110 min. The mixture was then filtered to separate the solid and liquid components. After solid-liquid separation, 24.9 L of wet solid A and liquid B were obtained.

[0211] 6 kg of adsorbent was added to the chromatography column, with an adsorption rate of 5 Bv / h. During elution, purified water was used at a rate of 3 Bv / h, and 45.2 L of eluent was collected. The results were analyzed and calculated as follows:

[0212] Lead content: 0.28 mg / kg;

[0213] Arsenic content: 0.16 mg / kg;

[0214] Cadmium content: 0.30 mg / kg;

[0215] Mercury content: 0.061 mg / kg;

[0216] Copper content: 1.68 mg / kg;

[0217] Zinc content: 4.01 mg / kg;

[0218] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O 20 ) and verbascoside (C 29 H 36 O 15 The total is 0.37%.

[0219] (3) Preparation of dry paste

[0220] Solid A and senna leaves were added to the water wash solution and stirred for 90 minutes; then decocted for 25 minutes; the filtrate was concentrated after filtration to obtain 12.6 kg of dry extract.

[0221] (4) Grinding, sieving, and preparing capsules

[0222] The dried extract was pulverized, mixed with Angelica sinensis, and sieved. Empty capsules and capsule filling equipment were used to obtain laxative capsules.

[0223] Comparative Example 1 (Flocculation and Sedimentation Method)

[0224] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0225] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0226] Lead content: 9.3 mg / kg;

[0227] Arsenic content: 4.2 mg / kg;

[0228] Cadmium content: 0.8 mg / kg;

[0229] Mercury content: 0.22 mg / kg;

[0230] Copper content: 19.2 mg / kg;

[0231] Zinc content: 30.5 mg / kg;

[0232] (1) Grinding and sieving

[0233] First, senna leaves, cistanche and angelica are screened to remove visible foreign matter, and then crushed and passed through a 200-sieve.

[0234] (2) Processing of Cistanche deserticola

[0235] The pulverized and sieved Cistanche deserticola was added to 25 L of purified water, heated to 70 °C, and tartaric acid was added to adjust the pH to 2.5. The mixture was stirred for 100 min. After stirring, sodium hydroxide was added to adjust the pH to 9.5, and the mixture was stirred for 100 min. Then, the mixture was filtered to separate the solid and liquid components. After solid-liquid separation, 24.9 L of wet solid A and liquid B were obtained.

[0236] Add 8 kg of chitosan flocculant to liquid B, maintain the temperature at 60℃, stir for 60 minutes, filter, and collect the solution. The results were then analyzed and calculated.

[0237] Lead content: 2.20 mg / kg;

[0238] Arsenic content: 1.13 mg / kg;

[0239] Cadmium content: 0.24 mg / kg;

[0240] Mercury content: 0.065 mg / kg;

[0241] Copper content: 10.87 mg / kg;

[0242] Zinc content: 18.73 mg / kg;

[0243] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O20 ) and verbascoside (C 29 H 36 O 15 The total is 0.28%.

[0244] Comparative Example 2 (Macroporous Chelating Resin Method)

[0245] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0246] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0247] Lead content: 3.7 mg / kg;

[0248] Arsenic content: 2.8 mg / kg;

[0249] Cadmium content: 3.6 mg / kg;

[0250] Mercury content: 0.76 mg / kg;

[0251] Copper content: 17.5 mg / kg;

[0252] Zinc content: 32.1 mg / kg;

[0253] (1) Grinding and sieving

[0254] First, senna leaves, cistanche and angelica are screened to remove visible foreign matter, and then crushed and passed through a 200-sieve.

[0255] (2) Processing of Cistanche deserticola

[0256] The pulverized and sieved Cistanche deserticola was added to 25 L of purified water, heated to 75 °C, and tartaric acid was added to adjust the pH to 2.6. The mixture was stirred for 100 min. After stirring, sodium hydroxide was added to adjust the pH to 9.4, and the mixture was stirred for 110 min. The mixture was then filtered to separate the solid and liquid components. After solid-liquid separation, 24.9 L of wet solid A and liquid B were obtained.

[0257] 4 kg of macroporous chelating resin was added to the resin column, with an adsorption rate of 8 Bv / h. During elution, purified water was used at a rate of 5 Bv / h, and 56.7 L of eluent was collected. The results were analyzed and calculated as follows:

[0258] Lead content: 0.84 mg / kg;

[0259] Arsenic content: 0.69 mg / kg;

[0260] Cadmium content: 0.99 mg / kg;

[0261] Mercury content: 0.22 mg / kg;

[0262] Copper content: 5.53 mg / kg;

[0263] Zinc content: 14.4 mg / kg;

[0264] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O 20 ) and verbascoside (C 29 H 36 O 15 The total amount is 0.25%.

[0265] Comparative Example 3 (Supercritical Extraction)

[0266] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0267] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0268] Lead content: 7.8 mg / kg;

[0269] Arsenic content: 2.4 mg / kg;

[0270] Cadmium content: 0.7 mg / kg;

[0271] Mercury content: 0.55 mg / kg;

[0272] Copper content: 24.3 mg / kg;

[0273] Zinc content: 30.3 mg / kg;

[0274] Supercritical fluid extraction process: The entrainer is an ethanol solution with a concentration controlled at 60% and a dosage of 0.6 L. During the supercritical process, the pressure is controlled at 25 MPa, the temperature at 60℃, and the time at 150 min.

[0275] After supercritical fluid extraction, the Cistanche deserticola was analyzed and its composition was calculated.

[0276] Lead content: 4.03 mg / kg;

[0277] Arsenic content: 1.02 mg / kg;

[0278] Cadmium content: 0.36 mg / kg;

[0279] Mercury content: 0.32 mg / kg;

[0280] Copper content: 14.63 mg / kg;

[0281] Zinc content: 20.51 mg / kg;

[0282] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O 20 ) and verbascoside (C 29 H 36 O 15 The total is 0.21%.

[0283] Comparative Example 4 (γ-mercaptopropyl bonded silica gel method)

[0284] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0285] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0286] Lead content: 9.7 mg / kg;

[0287] Arsenic content: 2.1 mg / kg;

[0288] Cadmium content: 2.3 mg / kg;

[0289] Mercury content: 0.17 mg / kg;

[0290] Copper content: 18.5 mg / kg;

[0291] Zinc content: 22.4 mg / kg;

[0292] (2) Processing of Cistanche deserticola

[0293] The pulverized and sieved Cistanche deserticola was added to 28 L of purified water, heated to 70 °C, and tartaric acid was added to adjust the pH to 2.8. The mixture was stirred for 100 min. After stirring, sodium hydroxide was added to adjust the pH to 9.2, and the mixture was stirred for 100 min. Then, the mixture was filtered to separate the solid and liquid components. After solid-liquid separation, 28.9 L of wet solid A and liquid B were obtained.

[0294] 8 kg of γ-mercaptopropyl-bonded silica gel was added to the adsorption column, and the adsorption rate was 7 Bv / h. During elution, purified water was used at a rate of 5 Bv / h, and 60.3 L of eluent was collected. The results were analyzed and calculated as follows:

[0295] Lead content: 2.76 mg / kg;

[0296] Arsenic content: 0.75 mg / kg;

[0297] Cadmium content: 0.68 mg / kg;

[0298] Mercury content: 0.05 mg / kg;

[0299] Copper content: 12.2 mg / kg;

[0300] Zinc content: 13.8 mg / kg;

[0301] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O 20 ) and verbascoside (C 29 H 36 O 15 The total is 0.29%.

[0302] Comparative Example 5 Patent (201110148709.2) Technology

[0303] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0304] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0305] Lead content: 5.3 mg / kg;

[0306] Arsenic content: 2.4 mg / kg;

[0307] Cadmium content: 1.8 mg / kg;

[0308] Mercury content: 0.15 mg / kg;

[0309] Copper content: 23.1 mg / kg;

[0310] Zinc content: 25.4 mg / kg;

[0311] (2) Processing of Cistanche deserticola

[0312] The pulverized and sieved Cistanche deserticola was added to 30 L of purified water, heated to 72 °C, and tartaric acid was added to adjust the pH to 2.2. The mixture was stirred for 100 min. After stirring, sodium hydroxide was added to adjust the pH to 9.9, and the mixture was stirred for 100 min. Then, the mixture was filtered to separate the solid and liquid components. After solid-liquid separation, 29.9 L of wet solid A and liquid B were obtained.

[0313] Add 4 kg of mesoporous silica particles to liquid B, stir for 60 min, let stand for 30 min, filter, and then test and calculate:

[0314] Lead content: 1.04 mg / kg;

[0315] Arsenic content: 0.59 mg / kg;

[0316] Cadmium content: 0.37 mg / kg;

[0317] Mercury content: 0.03 mg / kg;

[0318] Copper content: 12.3 mg / kg;

[0319] Zinc content: 15.5 mg / kg;

[0320] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O 20 ) and verbascoside (C 29 H 36 O 15 The total is 0.26%.

[0321] Comparative Example 6 Patent (201210201503.6) Technology

[0322] 80kg of senna leaves, 10kg of angelica root, and 10kg of cistanche.

[0323] The metal ion content of Cistanche deserticola was tested and found to be as follows:

[0324] Lead content: 6.3 mg / kg;

[0325] Arsenic content: 2.5 mg / kg;

[0326] Cadmium content: 0.8 mg / kg;

[0327] Mercury content: 0.24 mg / kg;

[0328] Copper content: 26.4 mg / kg;

[0329] Zinc content: 24.4 mg / kg;

[0330] (2) Processing of Cistanche deserticola

[0331] The pulverized and sieved Cistanche deserticola was added to 30L of purified water, heated to 75℃, and tartaric acid was added to adjust the pH to 2.3. The mixture was stirred for 100min. After stirring, sodium hydroxide was added to adjust the pH to 9.7, and the mixture was stirred for 100min. Then, the mixture was filtered to separate the solid and liquid components. After solid-liquid separation, 29.9L of wet solid A and liquid B were obtained.

[0332] The Cistanche deserticola solution was processed according to the method described in patent (201210201503.6), filtered, and then tested and calculated:

[0333] Lead content: 1.23 mg / kg;

[0334] Arsenic content: 0.69 mg / kg;

[0335] Cadmium content: 0.11 mg / kg;

[0336] Mercury content: 0.03 mg / kg;

[0337] Copper content: 9.29 mg / kg;

[0338] Zinc content: 10.96 mg / kg;

[0339] High-performance liquid chromatography (HPLC) determined that both solid A and liquid B of Cistanche deserticola contained echinacoside (C). 35 H 46 O 20 ) and verbascoside (C 29 H 36 O 15 The total is 0.24%.

[0340] Experimental Example 1

[0341] 1. Materials

[0342] Normal group: No medication administered.

[0343] Control group: Tongbianling capsules (provided by Ningxia Duowei Pharmaceutical Co., Ltd.)

[0344] Experimental group: Tongbianling capsules (produced according to the production process of Example 1 of this invention).

[0345] 2 animals

[0346] Kunming mice, half male and half female, are classified as Class I animals.

[0347] 3 Data Processing

[0348] All research data are expressed as mean ± standard deviation (x ± s). The significance of differences between groups was compared using the t-method for continuous data and the chi-square test for categorical data. 2 Differences between groups were compared using SPSS version 20.0 statistical software.

[0349] 4. Experimental Methods (Effects on Defecation Time and Quantity in Mice)

[0350] Mice were randomly divided into three groups of 10 mice each. The mice were administered the drugs as shown in the table below, once daily for three consecutive days. The control group received the same volume of 0.5% CMC-Na solution. Thirty minutes after the last administration, the mice were fasted for 20 hours, and each mouse was administered 0.3 ml of 10% charcoal-soaked saline solution by gavage. The mice were then placed in plastic boxes for observation. The time and amount of defecation were recorded.

[0351] 5 Results

[0352] The results are shown in the table below.

[0353] Effects of Tongbianling Capsules on Defecation Time and Number in Mice

[0354] Group Number of items (items) Dosage (g / kg) Defecation time (min) Stool volume (g) normal group 10 0 324.54±43.5* 3.35±1.28 control group 10 0.25 227.14±27.9** 9.24±0.89** experimental group 10 0.25 228.36±33.2** 9.02±1.23**

[0355] Note: Compared with the control group, * indicates P < 0.01, and ** indicates P < 0.05.

[0356] The Ridit test showed that the lesions in the normal group were significantly different from those in the normal group (P<0.01); compared with the normal group, the lesions in both the control group and the experimental group were significantly reduced (P<0.05).

[0357] The results showed that both the control group and the experimental group had a significant stimulating effect on the defecation time and volume of mice, and the differences were statistically significant compared with the normal group (P<0.01).

[0358] The results showed that the dosage of the control group was consistent with that of the product described in this invention, and the protective effect against constipation was comparable. This indicates that the laxative capsules prepared in this invention have the same efficacy as traditional laxative capsules.

Claims

1. A method for preparing a pharmaceutical composition for treating constipation, wherein, The pharmaceutical composition is made from the following raw materials in parts by weight: 80% senna leaves, 10% angelica sinensis, and 10% cistanche deserticola; The method for preparing the pharmaceutical composition includes the following steps: 1) Grinding and sieving First, senna leaves, cistanche and angelica are sieved to remove visible foreign matter, and then crushed and sieved. 2) Processing of Cistanche deserticola After being crushed and sieved, Cistanche deserticola was extracted and then separated into solid A and liquid B. Liquid B was then adsorbed, and the eluted liquid B' was collected. Wherein: the elution liquid B' contains: Lead content: <2 mg / kg; Arsenic content: <0.4 mg / kg; Cadmium content: <0.4 mg / kg; Mercury content: <0.09 mg / kg; Copper content: <10mg / kg; Zinc content: <5mg / kg; The extraction process involves adding Cistanche deserticola to purified water, heating the mixture to 60-80℃, adding tartaric acid, adjusting the pH to 2-3, stirring for 80-120 minutes, adding sodium hydroxide to adjust the pH to 9-10, stirring for another 80-120 minutes, and then filtering to separate the solid and liquid components. The purified water usage is calculated as follows: WCistanche deserticola : Lpurified water = 1 kg : 2-3 L. The adsorption refers to: adding adsorbent to the chromatography column at an adsorption rate of 5 Bv / h; eluting with purified water at a rate of 3 Bv / h during the elution process, and collecting the water eluent; the amount of adsorbent used is: WCistanche : Wadsorbent = 1 kg : 0.1-0.3 kg. The height-to-diameter ratio of the chromatography column is 8-10:1; The adsorbent refers to: (1) Crush the jujube pits and plum shells (without kernels) separately, pass them through a 200-mesh sieve and mix them; add 10-15% hydrochloric acid solution, adjust the pH to 2.5-3, and stir for 30-50 min; add 20-25% sodium hydroxide, adjust the pH to 9.5-10, stir for 30-50 min, then filter, separate the solid and liquid, and dry to obtain the mixture; (2) Adjust the pH of purified water to 2.8-3.2, add the mixture and 4-methoxybenzamide respectively, heat to 60-80℃, add anhydrous aluminum trichloride, and continue stirring for 100-120 min; after cooling to room temperature, filter, wash the wet solid twice with purified water and then dry. Purified water usage: Wmixture : Lpurified water = 1 kg : 4-8 L; Dosage of 4-methoxybenzamide: W mixture : W4-methoxybenzamide = 1 kg : 1.2-1.6 kg; Anhydrous aluminum trichloride dosage: Wmixture : Wanhydrous aluminum trichloride = 1 kg : 6-10 g; The amount of purified water used in the washing process is: Wmixture : Lpurified water = 1 kg : 11-15 L; (3) After drying, the solid is crushed and sieved, sodium bentonite is added, and after stirring evenly, purified water is added and stirring is continued to make a soft material, which is then passed through a 150-mesh sieve and placed in a crucible. Sodium-based bentonite dosage: Wmixture : Wsodium-based bentonite = 1 kg : 60-80 g; Purified water dosage: W mixture : L purified water = 1 kg : 80-100 ml; (4) Place the crucible in a muffle furnace and heat it from room temperature to 220-240℃ at a rate of 20℃ / min for 40-60 min for carbonization. Remove the crucible, allow it to cool naturally to room temperature, and pass it through a 150-mesh sieve to obtain the composite adsorbent; 3) Preparation of dry paste Solid A and senna leaves are added to the elution liquid B' and stirred for 80-120 minutes; then decocted for 20-30 minutes; after filtration, the filtrate is concentrated to obtain a dry extract; the amount of purified water used is: WCistanche:Lpurified water = 1 kg:3-5 L; the decoction refers to controlling the temperature at 90-100℃ and the time at 60-80 minutes, and decocting 2-3 times; 4) Grinding, sieving, and capsule preparation The dried extract was pulverized, mixed with Angelica sinensis, and sieved. Empty capsules and capsule filling equipment were used to obtain laxative capsules.

2. The method for preparing the pharmaceutical composition according to claim 1, characterized in that... The crushing and sieving mentioned in step 1) refers to: using a crusher to crush each raw material and passing it through a 200-mesh sieve.

3. The use of the pharmaceutical composition prepared by the method of claim 1 in the preparation of a medicine for treating constipation.

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