Pharmaceutical composition for treating gastrointestinal motility disorder and preparation method thereof

Abstract

The invention discloses a pharmaceutical composition for treating gastrointestinal motility disorder and a preparation method thereof, and belongs to the technical field of medicines. The effective components of the pharmaceutical composition are rhein and glycyrrhizic acid, and the mass ratio of the rhein to the glycyrrhizic acid is 1: 20. The invention has the following beneficial effects: research finds that mixed use of rhein and glycyrrhizic acid can greatly improve gastrointestinal motility, especially when rhein and glycyrrhizic acid are mixed according to a mass ratio of 1: 20, the gastrointestinal motility promotion effect is optimal.

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition and a preparation method thereof, in particular to a pharmaceutical composition for treating gastrointestinal motility disorders and a preparation method thereof, and belongs to the field of medical technology. Background Art

[0002] Gastrointestinal motility disorders are common and frequently occurring diseases among the elderly, especially those associated with organic diseases such as peptic ulcers, chronic gastritis, and trauma. Surveys in recent years have found that the incidence of gastrointestinal motility disorders is getting younger and younger, and is related to work, study pressure, and irregular eating habits. Therefore, gastrointestinal motility disorders have become a hot topic of concern for scholars at home and abroad, and they are constantly being explored and studied.

[0003] At present, the treatment of gastrointestinal motility disorders is mainly drug therapy. Most of the drugs used in clinical treatment are domperidone, cisapride, etc. These drugs have obvious effects in promoting gastrointestinal motility, but there are many adverse reactions, such as abdominal pain, diarrhea, headache, fatigue, dry mouth, etc. Therefore, the development of new gastrointestinal motility drugs is of great significance. Summary of the invention

[0004] In order to overcome the deficiencies of the prior art, the present invention aims to provide a pharmaceutical composition and a preparation method thereof which has significant therapeutic effects on gastrointestinal motility disorders and has no obvious side effects.

[0005] In order to achieve the above object, the present invention adopts the following technical solution:

[0006] A pharmaceutical composition for treating gastrointestinal motility disorders, wherein the active ingredients of the pharmaceutical composition are rhein and glycyrrhizic acid, and the mass ratio of rhein to glycyrrhizic acid is 1:20.

[0007] Preferably, the auxiliary ingredients of the pharmaceutical composition are lactose, starch and magnesium stearate, and the mass ratio of lactose, starch and magnesium stearate is 80:3:1; more preferably, the mass ratio of the active ingredient to the auxiliary ingredients of the pharmaceutical composition is 35:112.

[0008] The preparation method of the aforementioned pharmaceutical composition for treating gastrointestinal motility disorder comprises the following steps:

[0009] (1) Weigh rhein, glycyrrhizic acid, lactose, starch and magnesium stearate in a mass ratio of 1.25:25:80:3:1;

[0010] (2) putting rhein, glycyrrhizic acid, lactose and starch into a mixer and mixing them evenly, then adding an appropriate amount of water and continuing to mix until a uniform wet mixture is formed;

[0011] (3) drying the wet mixture in a fluidized bed dryer to a moisture content of 2.5%, and then sizing and sieving the dried granules to obtain uniform granules;

[0012] (4) Add magnesium stearate to the above granules and mix them evenly, then feed the mixed granules into a tablet press to obtain tablets.

[0013] The benefit of the present invention lies in that: research has found that the mixed use of rhein and glycyrrhizic acid can greatly improve gastrointestinal motility, especially when rhein and glycyrrhizic acid are mixed in a mass ratio of 1:20, the gastrointestinal motility promoting effect is the best. DETAILED DESCRIPTION

[0014] The present invention is described in detail below with reference to specific embodiments.

[0015] 1. Composition of the pharmaceutical composition

[0016] The effective ingredients of the pharmaceutical composition for treating gastrointestinal motility disorder provided by the present invention are rhein and glycyrrhizic acid, and the mass ratio of rhein to glycyrrhizic acid is 1:10-40.

[0017] 2. Efficacy of the drug combination on gastrointestinal motility disorders

[0018] 1. Materials

[0019] Mice: 80 Kunming mice, half male and half female, weighing 20±2 g, provided by Shandong Luye Pharmaceutical Co., Ltd., animal certificate number: scxk(Lu)20090009.

[0020] Rhein: Produced by Chengdu Desit Biotechnology Co., Ltd., product number DD0029.

[0021] Glycyrrhizic acid: produced by Chengdu Desit Biotechnology Co., Ltd., product number DG0006.

[0022] Cisapride tablets: produced by Zhejiang Jingxin Pharmaceutical Co., Ltd., batch number 1901161.

[0023] Atropine sulfate injection: produced by Tianjin Jinyao Amino Acid Co., Ltd., specification 0.5 mg / ml / vial, batch number 1712101.

[0024] Dextran blue (BD) 2000: produced by Pnarmacia, Sweden.

[0025] 2. Gastrointestinal propulsion experiment on mice

[0026] A total of 80 Kunming mice fasted for 24 hours were randomly divided into 8 groups (normal control group, atropine model group, cisapride group, rhein group, glycyrrhizic acid group, oxalic acid 1:10 group, oxalic acid 1:20 group, and oxalic acid 1:40 group), with 10 mice in each group.

[0027] First, each group was gavaged with 0.2 ml / 10 g, among which the normal control group was gavaged with distilled water, the atropine model group was gavaged with atropine sulfate injection, the cisapride group was gavaged with cisapride (the cisapride tablets were ground into powder and dissolved in distilled water to make the concentration of cisapride 0.15 mg / ml), the rhein group was gavaged with rhein (rhein was dissolved in distilled water to make the concentration of rhein 0.05 mg / ml), the glycyrrhizic acid group was gavaged with glycyrrhizic acid (glycyrrhizic acid was dissolved in distilled water to make the concentration of glycyrrhizic acid 1 mg / ml), and the rhubarb acid 1:10 group was gavaged with rhubarb acid (rhein was dissolved in distilled water to make the concentration of glycyrrhizic acid 1 mg / ml). The two groups were given rhein and glycyrrhizic acid (rhein and glycyrrhizic acid were dissolved in distilled water at the same time, so that the concentration of rhein was 0.05 mg / ml and the concentration of glycyrrhizic acid was 0.5 mg / ml) by gavage, the rhein 1:20 group was given rhein and glycyrrhizic acid (rhein and glycyrrhizic acid were dissolved in distilled water at the same time, so that the concentration of rhein was 0.05 mg / ml and the concentration of glycyrrhizic acid was 1 mg / ml) by gavage, and the rhein 1:40 group was given rhein and glycyrrhizic acid (rhein and glycyrrhizic acid were dissolved in distilled water at the same time, so that the concentration of rhein was 0.05 mg / ml and the concentration of glycyrrhizic acid was 2 mg / ml) by gavage.

[0028] One hour after intragastric administration, the normal control group was intraperitoneally injected with an equal volume of normal saline, and the other groups were intraperitoneally injected with 1 mg / kg atropine sulfate injection. 20 minutes later, each group was intragastricly administered with 0.4 ml of 20 mg / ml dextran blue (BD) 2000 solution, and all mice were killed by cervical dislocation 20 minutes later.

[0029] After killing the mice, the whole stomach was quickly removed by laparotomy. The contents of the stomach were dissolved in 4 ml of distilled water and centrifuged at 3500 r / min for 15 min. The supernatant was measured with an enzyme-labeled instrument at a wavelength of 620 nm to measure the absorbance value (A1). Another test tube was filled with 0.4 ml of 20 mg / ml dextran blue (BD) 2000 solution, centrifuged under the same conditions, and the supernatant was measured with an enzyme-labeled instrument at a wavelength of 620 nm to measure the absorbance value (A2). The gastric emptying rate was calculated according to the following formula:

[0030] Gastric emptying rate = (1-A1 / A2) × 100%

[0031] When the whole stomach was removed by laparotomy, the whole intestine from the pyloric sphincter to the end of the intestine was quickly removed and placed on a glass plate moistened with physiological saline. The whole intestine was gently peeled off and laid flat without any traction. The distance from the pyloric sphincter to the front end of the pigment propulsion (intestinal propulsion distance, cm) and the distance from the pyloric sphincter to the end of the intestine (whole intestine length, cm) were quickly measured. The intestinal propulsion rate was calculated according to the following formula:

[0032] Intestinal propulsion rate = intestinal propulsion distance ÷ total intestinal length × 100%

[0033] 3. Statistical processing

[0034] The data of each group are expressed as mean ± standard deviation SPSS 13.0 statistical software was used for data processing, one-way analysis of variance was performed, and pairwise comparisons were made between groups.

[0035] 4. Results

[0036] Table 1 Effect of rhein and glycyrrhizic acid combination on gastric emptying rate and intestinal propulsion rate in mice with gastrointestinal motility disorders

[0037] Grouping Gastric emptying rate (%) Intestinal propulsion rate (%) Normal control group 89.1±7.4 56.9±9.4 Atropine model group 68.0±10.2** 33.8±8.6** Cisapride group <![CDATA[90.0±5.7 ▲▲ ]]> <![CDATA[57.8±5.4 ▲▲ ]]> Rhein group <![CDATA[77.1±5.4 ▲ ]]> <![CDATA[42.9±5.7 ▲ ]]> Glycyrrhizic acid group <![CDATA[76.8±7.0 ▲ ]]> <![CDATA[42.6±7.8 ▲ ]]> Yellow oxalic acid 1:10 group <![CDATA[83.0±5.4 ▲▲# ]]> <![CDATA[50.2±5.8 ▲# ]]> Yellow oxalic acid 1:20 group <![CDATA[86.5±7.8 ▲▲## ]]> <![CDATA[54.3±9.3 ▲▲## ]]> Yellow oxalic acid 1:40 group <![CDATA[83.8±6.6 ▲▲# ]]> <![CDATA[49.8±7.0 ▲# ]]>

[0038] Note: Compared with the normal control group, **P<0.01; compared with the atropine model group, ▲ P<0.05, ▲▲ P<0.01; compared with the rhein group, #P<0.05, ##P<0.01.

[0039] From Table 1, we can see that:

[0040] (1) In this experiment, mice were given intraperitoneal injections of atropine sulfate (atropine model group), which blocked the action of M receptors and caused the gastric emptying rate and intestinal propulsion rate of mice to be significantly lower than those of the normal control group (P < 0.01), indicating that the preparation of the gastrointestinal motility disorder animal model by atropine sulfate injection was successful;

[0041] (2) The gastric emptying rate and intestinal propulsion rate of the cisapride group, rhein group, glycyrrhizic acid group, 1:10 oxalic acid group, 1:20 oxalic acid group, and 1:40 oxalic acid group were significantly higher than those of the atropine model group (P<0.05; P<0.01).

[0042] (3) Compared with the single use of rhein and glycyrrhizic acid, the gastric emptying rate and intestinal propulsion rate of the rhein 1:10 group, the rhein 1:20 group, and the rhein 1:40 group were significantly higher than those of the single use group (P < 0.05; P < 0.01).

[0043] (4) Among the 1:10, 1:20, and 1:40 groups of oxalic acid, the 1:20 group had the best effect in promoting gastric emptying rate and intestinal propulsion rate, and was the most effective in treating gastrointestinal motility disorders.

[0044] 3. Preparation method of pharmaceutical composition

[0045] For the convenience of taking, the pharmaceutical composition for treating gastrointestinal motility disorder provided by the present invention is made into tablets.

[0046] The active ingredients of the pharmaceutical composition are rhein and glycyrrhizic acid, and the mass ratio of rhein to glycyrrhizic acid is 1:20.

[0047] The auxiliary components of the pharmaceutical composition are lactose, starch and magnesium stearate, wherein lactose is used as a filler, starch is used as a binder, and magnesium stearate is used as a lubricant, and the mass ratio of lactose, starch and magnesium stearate is 80:3:1.

[0048] The mass ratio of the active ingredient to the auxiliary ingredient of the pharmaceutical composition is 35:112.

[0049] The preparation method of the tablet is specifically as follows:

[0050] (1) Accurately weigh 1.25 mg of rhein, 25 mg of glycyrrhizic acid, 80 mg of lactose, 3 mg of starch, and 1 mg of magnesium stearate;

[0051] (2) putting rhein, glycyrrhizic acid, lactose and starch into a mixer and mixing them evenly, then adding an appropriate amount of water and continuing to mix until a uniform wet mixture is formed;

[0052] (3) drying the wet mixture in a fluidized bed dryer to a moisture content of 2.5%, and then sizing and sieving the dried granules to obtain uniform granules;

[0053] (4) Magnesium stearate is added to the above granules and mixed evenly. The mixed granules are then fed into a tablet press and the parameters of the tablet press are adjusted to obtain tablets with a weight of 75±1.3 mg / tablet, a hardness of 120±3.5 N, and a disintegration time of 13.5±0.5 min.

[0054] It should be noted that the above embodiments are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the embodiments here. Any obvious changes or modifications derived from the technical solution of the present invention are still within the scope of protection of the present invention.

Claims

1. A pharmaceutical composition for treating gastrointestinal motility disorders, characterized in that: The active ingredients of the pharmaceutical composition are rhein and glycyrrhizic acid, and the mass ratio of rhein to glycyrrhizic acid is 1:

20.

2. The pharmaceutical composition for treating gastrointestinal motility disorders according to claim 1, characterized in that: The auxiliary components of the pharmaceutical composition are lactose, starch and magnesium stearate, and the mass ratio of lactose, starch and magnesium stearate is 80:3:

1.

3. The pharmaceutical composition for treating gastrointestinal motility disorders according to claim 2, characterized in that: The mass ratio of the active ingredient to the auxiliary ingredient of the pharmaceutical composition is 35:

112.

4. The method for preparing the pharmaceutical composition for treating gastrointestinal motility disorder according to claim 1, characterized in that: The following steps are involved: (1) Weigh rhein, glycyrrhizic acid, lactose, starch and magnesium stearate in a mass ratio of 1.25:25:80:3:1; (2) putting rhein, glycyrrhizic acid, lactose and starch into a mixer and mixing them evenly, then adding an appropriate amount of water and continuing to mix until a uniform wet mixture is formed; (3) drying the wet mixture in a fluidized bed dryer to a moisture content of 2.5%, and then sizing and sieving the dried granules to obtain uniform granules; (4) Add magnesium stearate to the above granules and mix them evenly, then feed the mixed granules into a tablet press to obtain tablets.