Pharmaceutical composition for treating slow transit constipation and application thereof

Abstract

The invention relates to the technical field of biological medicines, in particular to a pharmaceutical composition for treating slow transit constipation and application of the pharmaceutical composition. The pharmaceutical composition for treating slow transit constipation provided by the invention is simple in component and good in safety, can give full play to the synergistic effect of medicines, has a remarkable treatment effect on slow transit constipation, and can solve the problems of more components and insufficient curative effect when a pharmaceutical composition in the prior art is used for treating slow transit constipation.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to a pharmaceutical composition for treating slow-transmission constipation and an application thereof. Background Art

[0002] Constipation is a common digestive system disease, mainly manifested by symptoms such as reduced bowel movements, hard and dry stools, and difficulty in defecation. According to its causes and duration, constipation can be divided into two categories: acute constipation and chronic constipation. Slow transit constipation (STC) is a special type of chronic constipation, characterized by colonic transit dysfunction, abnormally slow movement of food residues in the intestine, and clinical manifestations such as reduced bowel movements (spontaneous bowel movements <3 times / week), labored defecation, and hard and dry stools. As the disease progresses, patients may experience incomplete obstruction symptoms such as abdominal pain and bloating, and even fecal stone colon obstruction in severe cases. The incidence of STC is affected by social factors such as the accelerated pace of life, changes in eating habits, and an aging population, and is showing a gradual upward trend. This not only seriously affects the work and life of patients, but also increases the socioeconomic burden.

[0003] The treatment of STC is relatively complex and requires a personalized treatment plan based on the patient's specific situation. Currently, the clinical treatment effect of STC is not ideal. Clinical drug treatment mainly uses osmotic laxatives (such as polyethylene glycol) and stimulant laxatives (such as bisacodyl) to promote defecation.

[0004] CN114306494B proposes a prescription, including honey, liquorice, scutellaria, costusroot, white peony root, angelica, rhubarb, hemp seed, aloe and multiple ingredients. Through the mutual cooperation of each component, the effects of tonifying the kidney and activating blood circulation, moistening the intestine and relieving constipation, tonifying the middle and replenishing qi, and improving the symptoms of asthenic constipation are achieved. CN116832084B provides a composition for treating constipation and a preparation method thereof, the composition includes hemp seed oil, water extract, alcohol extract, fermentation embedded particles and lactulose and other ingredients, which can relieve chronic constipation, improve the health of the intestine, increase the frequency of active defecation of patients, improve the stool form and relieve abdominal distension symptoms, and play the effect of preventing and treating constipation. The above-mentioned prior arts all contain multiple components with limited sources, and there are too many components in the composition, which is not convenient for industrial production and cannot meet the growing demand.

[0005] Therefore, it is necessary to invent a pharmaceutical composition for treating slow-transmission constipation that has few components and is easy to produce. Summary of the invention

[0006] In response to the existing technical problems, the present invention aims to provide a pharmaceutical composition for treating slow-transmission constipation and its application. This composition has simple components and good safety, can give full play to the synergistic effect between drugs, has a significant therapeutic effect on slow-transmission constipation, and can solve the problem of more components and insufficient efficacy of pharmaceutical compositions in the prior art for treating slow-transmission constipation.

[0007] The invention discloses a pharmaceutical composition for treating slow-transmission constipation. The components of the pharmaceutical composition include bisacodyl and atractylodes macrocephala.

[0008] Preferably, the dosage of bisacodyl is 3 to 5 mg / d.

[0009] Preferably, the dosage of Atractylodes macrocephala is 30 to 60 g / d.

[0010] Preferably, the further dose of bisacodyl is 5 mg / d.

[0011] Preferably, the dosage of Atractylodes macrocephala is 60 g / d.

[0012] An application of a pharmaceutical composition for treating slow-transmission constipation comprises the following steps:

[0013] S1 Establishment of rat model of slow-transmission constipation: 70 SPF SD rats were selected and adaptively raised for 1 week. 8 rats were randomly selected as blank control group. The blank control group was given pure water by gavage, 10 ml / kg / d per rat; the remaining rats were modeled and given 15 mg / kg compound diphenoxylate suspension by gavage once a day for 14 consecutive days to establish a rat model of slow-transmission constipation;

[0014] S2 Grouping and administration: The rat models were randomly divided into model group, bisacodyl group, Atractylodes macrocephala group, and bisacodyl and Atractylodes macrocephala combination group, with 8 rats in each group. The equivalent dose for rats was calculated based on the body surface area of ​​humans and animals. The rats were given intragastrically once a day for 14 consecutive days.

[0015] S3 efficacy evaluation: observe and record the number of feces particles, feces water content and the time of first black stool discharge of rats 24 hours after 14 days of drug administration.

[0016] Preferably, the significance index of fecal particle number of rats in the bisacodyl and Atractylodes macrocephala combination group is P < 0.001.

[0017] Preferably, the significance index of feces moisture content of rats in the bisacodyl and Atractylodes macrocephala combination group is P<0.001.

[0018] Preferably, the significance index of the time of first black stool excretion of rats in the bisacodyl and Atractylodes macrocephala combination group is P<0.001.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] The present invention provides a pharmaceutical composition for treating slow-transmission constipation with simple components and significant efficacy. Its core advantage lies in the ingenious combination of the main ingredients bisacodyl and Atractylodes macrocephala, which is an effective combination of Chinese and Western medicine. The combination of the two not only shows a significant improvement in the treatment of slow-transmission constipation, but also greatly optimizes the economy and safety of drug use. Compared with single medication, combined use can significantly reduce the dosage of bisacodyl and Atractylodes macrocephala, effectively reduce the intestinal dependence on drugs, and reduce the risk of potential drug side effects.

[0021] In addition, the innovation of this drug combination lies in the simplicity and availability of its components and their synergistic effects. Bisacodyl, as a stimulant laxative, can accelerate intestinal peristalsis; Atractylodes macrocephala has the effects of strengthening the spleen and replenishing qi, drying dampness and promoting diuresis, and helps to improve the intestinal environment. The two complement each other, not only simplifying the treatment plan, but also improving the overall efficacy, providing patients with a safer, more effective and economical constipation treatment option. The emergence of this innovative combination has undoubtedly brought new breakthroughs and hope to the treatment of slow-transmission constipation. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 : Bar graph of rat feces particle count in blank control group and each embodiment

[0024] Figure 2 : Bar graph of water content of rat feces in blank control group and each embodiment

[0025] Figure 3 : Bar graph of time of first black stool discharge in rats in blank control group and each embodiment DETAILED DESCRIPTION

[0026] The following examples are provided for a better understanding of the present invention, but are not intended to limit the best mode of implementation, nor to limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior arts shall fall within the protection scope of the present invention.

[0027] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be obtained commercially.

[0028] The data results of this experiment are expressed as mean ± standard deviation (mean ± SD). The inter-group comparison was performed using GraphPadPrism 8.0 software to perform One-way ANOVA analysis (single-factor analysis of variance) to examine the significance, with P < 0.05 as the significance index. The P value is used to determine whether the difference between the groups is statistically significant. * indicates a significant difference between the model group and the control group. # Indicates a significant difference between the drug-treated group and the model group. One * or # Indicates P < 0.05, two * or # indicates P < 0.01, and three * or # indicate P < 0.001.

[0029] An application of a pharmaceutical composition for treating chronic transit constipation comprises the following steps:

[0030] Establishment of the S1 slow-transmission constipation rat model:

[0031] 70 specific pathogen-free (SPF) SD rats were selected and adaptively raised for 1 week. Eight rats were randomly selected as the blank control group, and the blank control group was given pure water by gavage, 10 mL / kg / d per rat. The remaining rats were modeled and given 15 mg / kg of compound diphenoxylate suspension by gavage once a day for 14 consecutive days to establish a rat model of slow-transmission constipation.

[0032] S2 group administration:

[0033] The rat models were randomly divided into model group, bisacodyl group, Atractylodes macrocephala group, bisacodyl and Atractylodes macrocephala combination group 1, bisacodyl and Atractylodes macrocephala combination group 2, and bisacodyl and Atractylodes macrocephala combination group 3, with 8 rats in each group. The equivalent dose of rats was calculated based on the body surface area of ​​humans and animals. The rats were given the drug by gavage once a day for 14 consecutive days. The drug administration is shown in the following table:

[0034]

[0035] S3 efficacy evaluation:

[0036] (1) General condition: Observe and record the rats' activity, mental state, food intake, fur color, body weight before and after treatment, and the number of feces particles and feces weight 24 hours after 14 days of administration.

[0037] (2) Determination of fecal moisture content: 14 days after administration, the wet feces of the rats were weighed for 24 hours, and then the dry feces were weighed after drying in a 90°C drying oven for 3 hours, and the fecal moisture content (%) of the rats before and after administration was calculated. Fecal moisture content (%) = (wet feces mass - dry feces mass) / wet feces mass × 100%.

[0038] (3) Defecation: One week after the rats stopped taking the drug, the time of first black stool discharge was determined by intragastric administration of activated carbon. The rats were fasted for 24 h but not water, and then intragastrically administered with 2 ml of 100 g / L activated carbon suspension. The time from intragastric administration to the discharge of the first black stool was recorded.

[0039] The administration results of the blank control group and Examples 1 to 6 are shown in the following table:

[0040] (1) Effect of bisacodyl and Atractylodes macrocephala on the number of fecal particles in rats:

[0041] Table 1: Comparison of fecal pellet numbers in each group of rats (mean ± SD)

[0042] Group Number of animals Number of fecal particles (particles / day) Blank control group 8 55.75±3.77 Example 1: Model group 8 33.38±3.50*** Example 2: Bisacodyl Group 8 <![CDATA[41.88±2.93 ## ]]> Example 3: Atractylodes macrocephala group 8 <![CDATA[40.75±4.24 # ]]> Example 4: Bisacodyl and Atractylodes macrocephala combination group 1 8 <![CDATA[50.75±6.04 ### ]]> Example 5: Bisacodyl and Atractylodes macrocephala combination group 2 8 <![CDATA[52.88±3.62 ### ]]> Example 6: Bisacodyl and Atractylodes macrocephala combination group 3 8 <![CDATA[54.50±6.98 ### ]]>

[0043] As shown in Table 1, compared with the rats in the blank control group, the feces pellet number of the model group rats in Example 1 was significantly reduced (P < 0.001); compared with the rats in the model group of Example 1, bisacodyl alone and Atractylodes macrocephala alone increased the feces pellet number of the rats in the bisacodyl group of Example 2 and the Atractylodes macrocephala group of Example 3 to different degrees (P < 0.01, P < 0.05); compared with the rats in the model group of Example 1, different doses of bisacodyl and Atractylodes macrocephala combined use in the bisacodyl and Atractylodes macrocephala combined use groups of Examples 4 to 6 could significantly increase the feces pellet number of the rats (P < 0.001), showing a synergistic effect and a dose-dependent improvement trend.

[0044] (2) Effect of bisacodyl and Atractylodes macrocephala on the water content of rat feces:

[0045] Table 2: Comparison of feces water content of rats in each group (mean ± SD)

[0046] Group Number of animals Feces moisture content (%) Blank control group 8 45.07±3.18 Example 1: Model group 8 36.62±2.20*** Example 2: Bisacodyl Group 8 <![CDATA[42.29±2.35 ## ]]> Example 3: Atractylodes macrocephala group 8 39.66±1.94 Example 4: Bisacodyl and Atractylodes macrocephala combination group 1 8 <![CDATA[45.97±2.66 ### ]]> Example 5: Bisacodyl and Atractylodes macrocephala combination group 2 8 <![CDATA[45.77±3.44 ### ]]> Example 6: Bisacodyl and Atractylodes macrocephala combination group 3 8 <![CDATA[45.14±2.71 ### ]]>

[0047] As shown in Table 2 above, compared with the rats in the blank control group, the feces moisture content of the model group rats in the model group of Example 1 was significantly reduced (P < 0.001); compared with the rats in the model group of Example 1, the feces moisture content of the rats in the bisacodyl group of Example 2 and the Atractylodes group of Example 3 was significantly improved (P < 0.01), and the feces moisture content of the rats in the Atractylodes group was not significantly improved; compared with the rats in the model group of Example 1, the feces moisture content of the rats in the bisacodyl and Atractylodes combination groups of Examples 4 to 6 at different doses of bisacodyl and Atractylodes combination was significantly increased, showing a synergistic effect (P < 0.001), and there was no significant difference between the combination groups.

[0048] (3) Effect of bisacodyl and Atractylodes macrocephala on the time of first black stool discharge in rats:

[0049] Table 3: Comparison of the time of first black stool discharge in rats of each group (mean ± SD)

[0050]

[0051]

[0052] As shown in Table 2, compared with the rats in the blank control group, the model group of Example 1 had a significantly prolonged time to discharge the first black stool in the rats in the model group (P < 0.001); compared with the rats in the model group of Example 1, the bisacodyl group of Example 2 and the Atractylodes macrocephala group of Example 3 had different degrees of improvement on the time to discharge the first black stool in the rats (P < 0.01, P < 0.05); compared with the rats in the model group of Example 1, the bisacodyl and Atractylodes macrocephala combination groups of Examples 4 to 6 had different doses of bisacodyl and Atractylodes macrocephala combination that significantly shortened the time to discharge the first black stool in the rats (P < 0.01, P < 0.001), and there was a trend of dose-dependent improvement.

[0053] The above results show that the combination of bisacodyl and Atractylodes macrocephala has a synergistic effect, can accelerate intestinal transit, and has a significant synergistic effect in the treatment of rats with slow-transit constipation.

[0054] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived from these are still within the scope of protection of the invention.

Claims

1. A pharmaceutical composition for treating slow-transmission constipation, characterized in that: The components of the pharmaceutical composition include bisacodyl and Atractylodes macrocephala.

2. A pharmaceutical composition for treating slow-transmission constipation according to claim 1, characterized in that: The dosage of bisacodyl is 3 to 5 mg / d.

3. A pharmaceutical composition for treating slow-transmission constipation according to claim 1, characterized in that: The dosage of Atractylodes macrocephala is 30 to 60 g / d.

4. A pharmaceutical composition for treating slow-transmission constipation according to claim 1, characterized in that: The dosage of bisacodyl is 5 mg / d.

5. A pharmaceutical composition for treating slow-transmission constipation according to claim 1, characterized in that: The dosage of Atractylodes macrocephala is 60g / d.

6. Use of a pharmaceutical composition for treating chronic transit constipation, characterized in that: The following steps are involved: S1 Establishment of rat model of slow-transmission constipation: 70 SPF SD rats were selected and adaptively raised for 1 week. 8 rats were randomly selected as blank control group. The blank control group was given pure water by gavage, 10 ml / kg / d per rat; the remaining rats were modeled and given 15 mg / kg compound diphenoxylate suspension by gavage once a day for 14 consecutive days to establish a rat model of slow-transmission constipation; S2 Grouping and administration: The rat models were randomly divided into model group, bisacodyl group, Atractylodes macrocephala group, and bisacodyl and Atractylodes macrocephala combination group, with 8 rats in each group. The equivalent dose for rats was calculated based on the body surface area of ​​humans and animals. The rats were given intragastrically once a day for 14 consecutive days. S3 efficacy evaluation: observe and record the number of feces particles, feces water content and the time of first black stool discharge of rats 24 hours after 14 days of drug administration.

7. A pharmaceutical composition for treating chronic transit constipation according to claim 1, characterized in that: The significance index of the number of feces particles of rats in the bisacodyl and Atractylodes macrocephala combination group was P < 0.

001.

8. A pharmaceutical composition for treating chronic transit constipation according to claim 1, characterized in that: The significance index of feces moisture content of rats in the bisacodyl and Atractylodes macrocephala combination group was P<0.

001.

9. A pharmaceutical composition for treating chronic transit constipation according to claim 1, characterized in that: The significance index of the time of first black stool discharge of rats in the bisacodyl and Atractylodes macrocephala combination group was P<0.001.

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