A pharmaceutical composition for treating gastrointestinal motility disorders and a preparation method thereof

Abstract

The present invention discloses a pharmaceutical composition for treating gastrointestinal motility disorders and a preparation method thereof, belonging to the field of medical technology. The active ingredients of the pharmaceutical composition are rhein and glycyrrhizic acid, with the mass ratio of rhein to glycyrrhizic acid being 1:20. The present invention is beneficial in that research has found that combining rhein and glycyrrhizic acid can significantly improve gastrointestinal motility, with the most effective effect being achieved when the mass ratio of rhein and glycyrrhizic acid is 1:20.

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, belonging to the technical field of medicine. Background Art

[0002] Gastrointestinal motility disorders are common and frequently occurring in the elderly, particularly those associated with organic diseases such as peptic ulcers, chronic gastritis, and trauma. Recent studies have found that the incidence of gastrointestinal motility disorders is increasingly younger, with associations such as work and study stress and irregular dietary habits. Consequently, gastrointestinal motility disorders have become a hot topic of research, attracting ongoing exploration and study by scholars both domestically and internationally.

[0003] Currently, the main treatment for gastrointestinal motility disorders is medication, with domperidone and cisapride being the most commonly used drugs in clinical practice. While these drugs are effective in promoting gastrointestinal motility, they can also cause numerous adverse reactions, such as abdominal pain, diarrhea, headache, fatigue, and dry mouth. Therefore, the development of new gastrointestinal motility drugs is of great significance. Summary of the Invention

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

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

[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 ingredient of the pharmaceutical composition is 35:112.

[0008] The method for preparing the aforementioned pharmaceutical composition for treating gastrointestinal motility disorders 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) Magnesium stearate is added to the above granules and mixed evenly, and then the mixed granules are fed into a tablet press to obtain tablets.

[0013] The benefit of the present invention lies in that: research has found that mixing rhein and glycyrrhizic acid can greatly improve gastrointestinal motility, and the gastrointestinal motility-promoting effect is best when rhein and glycyrrhizic acid are mixed in a mass ratio of 1:20. 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 pharmaceutical composition for treating gastrointestinal motility disorders provided by the present invention comprises rhein and glycyrrhizic acid as active ingredients, and the mass ratio of rhein to glycyrrhizic acid is 1:10-40.

[0017] 2. Efficacy of the pharmaceutical composition for 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 Desite Biotechnology Co., Ltd., product number DD0029.

[0021] Glycyrrhizic acid: produced by Chengdu Desite 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 0.5mg / ml / vial, batch number 1712101.

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

[0025] 2. Gastrointestinal propulsion experiment on mice

[0026] Eighty Kunming mice fasted for 24 hours were randomly divided into eight groups (normal control group, atropine model group, cisapride group, rhein group, glycyrrhizic acid group, oxaloxalic acid 1:10 group, oxaloxalic acid 1:20 group, and oxaloxalic 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 rhein group was gavaged with rhein (rhein was dissolved in distilled water to make the concentration of glycyrrhizic acid 1:10). The rats were given rhein and glycyrrhizic acid (rhein and glycyrrhizic acid were dissolved in distilled water at the same time to make the concentration of rhein 0.05 mg / ml and glycyrrhizic acid 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 to make the concentration of rhein 0.05 mg / ml and glycyrrhizic acid 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 to make the concentration of rhein 0.05 mg / ml and glycyrrhizic acid 2 mg / ml) by gavage.

[0028] One hour after oral 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. Twenty minutes later, each group was given 0.4 ml of 20 mg / ml dextran blue (BD) 2000 solution by oral gavage, and all mice were killed by cervical dislocation 20 minutes later.

[0029] After killing the mice, the entire stomach was quickly removed by laparotomy. The stomach contents were dissolved in 4 ml of distilled water and centrifuged at 3500 rpm for 15 min. The absorbance of the supernatant was measured at 620 nm using a microplate reader (A1). Another test tube was filled with 0.4 ml of 20 mg / ml Dextran Blue (BD) 2000 solution and centrifuged under the same conditions. The absorbance of the supernatant was measured at 620 nm using a microplate reader (A2). The gastric emptying rate was calculated using the following formula:

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

[0031] The entire stomach was removed by laparotomy. The entire intestine from the pyloric sphincter to the intestinal end was quickly removed and placed on a glass plate moistened with physiological saline. The intestine was gently peeled off and flattened 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 intestinal end (total intestinal 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 and one-way analysis of variance was performed, with pairwise comparisons between groups.

[0035] 4. Results

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

[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 injected intraperitoneally with atropine sulfate (atropine model group), which blocked the action of M receptors. The gastric emptying rate and intestinal propulsion rate of the mice were 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, rhein 1:20 group, and 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 oxalic acid groups, the 1:20 oxalic acid group had the best effect in promoting gastric emptying rate and intestinal propulsion rate, and had the best effect 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 disorders provided by the present invention is prepared 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 was added to the above granules and mixed evenly. The mixed granules were then fed into a tablet press and the parameters of the tablet press were 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 the purpose of clearly illustrating the present invention and are not intended to limit the embodiments of the present invention. A person skilled in the art would be able to make other variations or modifications based on the above description. It is not possible to enumerate all embodiments here. Any obvious variations or modifications arising from the technical solution of the present invention remain 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 disorders 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) Magnesium stearate is added to the above granules and mixed evenly, and then the mixed granules are fed into a tablet press to obtain tablets.