Composition of piveronium bromide and fructus rosae laevigatae extract as well as preparation process and application of composition

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a composition of piveronium bromide and a cherokee rose fruit extract, a preparation process and application. The tablet is composed of piveronium bromide, a rosa laevigata michx extract, a disintegrating agent, a lubricant and a filler, and pharmacological experiments of rats find that the tablet has a significant treatment effect on diarrhea-type irritable bowel syndrome, can be completely dissolved out within 15 min, has low content of related substances, is higher than the requirements of pharmacopeia, and is suitable for further industrial mass production.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a composition of pinaverium bromide and a Rosa laevigata fruit extract, a preparation process and uses thereof. Background Art

[0002] Pinaverium bromide was developed by the French pharmaceutical company Solvay and first launched on the market in 1975. Its structural formula is as follows:

[0003]

[0004] Pinaverium bromide is a calcium antagonist with highly selective antispasmodic effects in the gastrointestinal tract. Its mechanism of action on smooth muscle is similar to that of other calcium antagonists, but it is highly selective for colonic smooth muscle. Pinaverium bromide achieves its antispasmodic effect by blocking the influx of calcium ions into intestinal smooth muscle cells, preventing excessive muscle contraction. This eliminates intestinal smooth muscle hyperreactivity and increases intestinal motility.

[0005] The Latin name of Rosa laevigata is Rosalaevigata Michx. It has a long history of medicinal use and is recorded in ancient medical classics such as "Compendium of Materia Medica", "Chinese Materia Medica", "Lingnan Herbal Medicine", "Jiangxi Folk Herbal Prescriptions", and "Hunan Herbal Medicine". It is widely distributed in Guangxi, Guangdong, Hunan and other places. It is the main raw material of Fuke Qianjin Tablets, Jinji Capsules, Sanjin Tablets, and Wanglaoji Herbal Tea. The chemical composition of its roots is mainly triterpenoid saponins, flavonoids, and carbohydrates, but current research on its material basis and mechanism of action is not in-depth.

[0006] In the prior art, there is no report of preparing pinaverium bromide and Rosa laevigata fruit into a pharmaceutical composition for use, and even less of preparing the two into tablets for use in related experiments. Summary of the Invention

[0007] Based on the deficiencies of the existing technology, a composition, preparation process and use of pinaverium bromide and Rosa laevigata extract are provided, which solves the problem that the active substance of pinaverium bromide is unstable during storage and easily decomposes when exposed to light or heat, and is suitable for further large-scale industrial production.

[0008] Specifically, the inventors solved the problem through the following technical solutions:

[0009] The first object of the present invention is to provide a tablet containing pinaverium bromide, which contains the following raw materials: 10 parts by weight of pinaverium bromide, 0.5-1.5 parts by weight of Rosa laevigata extract, 2-10 parts by weight of disintegrant, 0.1-1.1 parts by weight of lubricant, and 40-130 parts by weight of filler.

[0010] Furthermore, the pinaverium bromide tablet contains the following raw materials: 10 parts by weight of pinaverium bromide, 1 part by weight of Rosa laevigata extract, 3 parts by weight of disintegrant, 0.6 parts by weight of lubricant, and 85 parts by weight of filler.

[0011] Furthermore, the filler is selected from one or two of microcrystalline cellulose, lactose, mannitol, and starch; more preferably, the filler is selected from a combination of microcrystalline cellulose and lactose.

[0012] In a preferred embodiment of the present invention, the ratio of microcrystalline cellulose to lactose is 2-6:2-7 by weight; more preferably, the ratio of microcrystalline cellulose to lactose is 8:9.

[0013] Furthermore, the disintegrant is selected from one of low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch, preferably sodium carboxymethyl starch; the lubricant is selected from any one of magnesium stearate, talc, and sodium lauryl sulfate, preferably magnesium stearate.

[0014] In a preferred embodiment of the present invention, the pinaverium bromide tablets contain the following raw materials: 10 parts by weight of pinaverium bromide, 0.5-1.5 parts by weight of Rosa laevigata extract, 2-10 parts by weight of sodium carboxymethyl starch, 0.1-1.1 parts by weight of magnesium stearate, 20-60 parts by weight of microcrystalline cellulose, and 20-70 parts by weight of lactose.

[0015] In a preferred embodiment of the present invention, the pinaverium bromide tablets contain the following raw materials: 10 parts by weight of pinaverium bromide, 1 part by weight of Rosa laevigata extract, 3 parts by weight of sodium carboxymethyl starch, 0.6 parts by weight of magnesium stearate, 40 parts by weight of microcrystalline cellulose, and 45 parts by weight of lactose.

[0016] In a preferred embodiment of the present invention, the pinaverium bromide tablets may be further coated.

[0017] The second object of the present invention is to provide a method for extracting the Rosa Laevigata extract:

[0018] 1) Take the Rosa laevigata fruit pulp powder, add 30-60% sodium chloride and soak for 30-50 minutes, then heat to 70-80°C to extract the medicinal liquid, and set aside the medicinal residue and the extract;

[0019] 2) Repeat step 1) with the medicinal residue and extract twice; combine the filtrates from the three extractions;

[0020] 3) collecting the filtrate from step 2), concentrating under reduced pressure at 50-60° C. to an alcohol content of 80-90%; standing at room temperature for 24 hours, centrifuging, and collecting the precipitate and supernatant to obtain the Rosa laevigata extract;

[0021] 4) Deproteinizing the polysaccharide extract obtained in step 3) by the Sevag method, centrifuging, concentrating the supernatant, precipitating with ethanol, collecting the precipitate, and vacuum drying to obtain a Rosa laevigata extract.

[0022] Step 4) is specifically as follows: the protein of the Rosa laevigata extract obtained in step 3) is removed by the Sevag method, centrifuged, and the supernatant is concentrated. The mixed Rosa laevigata extract is added with 95% ethanol in a volume ratio of 1:4, placed in a refrigerator (4°C), and allowed to stand for 24 hours overnight. The mixture is centrifuged at 4000 rpm for 15 minutes, and the precipitate is collected and dissolved in an appropriate amount of deionized water to obtain the Rosa laevigata extract.

[0023] The third object of the present invention is to provide a method for preparing the pinaverium bromide tablets:

[0024] 1) Dissolve glyceryl monostearate in a mixture of chloroform and 95% or more ethanol, stirring continuously to mix thoroughly;

[0025] 2) adding pinaverium bromide to step 1) and mixing, stirring to dissolve;

[0026] 3) adding the Rosa laevigata extract evenly to the mixed solution of step 2), maintaining the temperature at 40-50° C. and rotary evaporating under reduced pressure to dryness, adding microcrystalline cellulose, lactose, and sodium carboxymethyl starch, blending, sieving, adding magnesium stearate, and tableting to obtain plain tablets;

[0027] 4) Weighing a coating premix powder and adding water to mix to prepare a film coating premix, film coating the above plain tablets to a coating weight gain of 3-10%, and drying to obtain tablets containing pinaverium bromide.

[0028] The coating premix is ​​weighed and added with water to prepare a film coating premix, which is then film coated on the plain tablets obtained in step (3) to a weight gain of 3-10%. The tablets are then dried at a material temperature of 35° C. and further dried until the free moisture content is below 3%, thereby obtaining tablets containing pinaverium bromide. The remaining coating solution can be recycled for use in the next batch.

[0029] The fourth object of the present invention is to mix the pinaverium bromide of the present invention with the extract of Rosa laevigata and provide the use of the pinaverium bromide tablets in the preparation of a medicament for treating diarrhea-type irritable bowel syndrome. The inventors created a method of using the Rosa laevigata extract in combination with pinaverium bromide. In a pharmacological experiment on rats, it was found that on the 21st and 35th days, the rats' novelty inhibition of feeding latency was significantly shortened in the Example 1-3 groups compared with the positive group, the Comparative Example 1 group, and the Comparative Example 2 group, and the D-lactic acid and serum TNF-α, IFN-γ, and IL-6 levels were significantly reduced, indicating that the combined use of pinaverium bromide and the Rosa laevigata extract of the present invention achieved unexpected technical effects.

[0030] The fifth object of the present invention is to provide a tablet containing Rosa Laevigata extract and Pinaverium bromide, wherein the dissolution of Pinaverium bromide in 15 minutes can be dissolved by more than 95%, which is better than the requirements of the pharmacopoeia. In the accelerated test at 0, 1, 2, 3, and 6 months, the solubility of Examples 1-5 under the conditions of pH 1.0 HCl solution was more than 99%, which is significantly higher than the dissolution requirements of the Chinese Pharmacopoeia. In the accelerated test, the solubility of Comparative Examples 1, 3, 4, 5, and 6 at 15 minutes was less than 85%, but Comparative Examples 3-5 were already less than 80%, which could not meet the requirements of the pharmacopoeia. At the same time, the Rosa Laevigata extract was optimized, and it was found that the pretreatment and extraction process had a greater impact on it; when a filler different from the present invention was selected, the Rosa Laevigata extract had varying degrees of degradation during storage.

[0031] The content of related substances of tablets of the present invention is low. The content of related substances of embodiments 1-5 is within 0.5%. Comparative Example 1 does not contain Rosa Laevigata extract. The extract is particularly important for the stability of Pinaverium Bromide. The inventor believes that polysaccharides can form a protective film on the surface of the drug. This film can isolate the contact of drug molecules with the external environment, slow down the influence of moisture, oxygen and light on Pinaverium Bromide, thereby reducing or avoiding the rate of hydrolysis reaction, thereby improving the stability of the drug. The Rosa Laevigata extract of Comparative Example 2 is too high, and other substances in it may react with Pinaverium Bromide to cause degradation. Comparative Example 6 adopts different extracts and also has an impact on the related substances of the final product. Comparative Example 5 adopts different preparation processes, and the difference in preparation processes has a greater impact on Pinaverium Bromide. It can be seen from this that Pinaverium Bromide is relatively sensitive to light, temperature and other adjuvants, and not taking relevant protection methods will accelerate its degradation. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 : Comparison of dissolution rates of each example at 0, 1, 2, 3 and 6 months.

[0033] Figure 2 : Comparison of related substances of each example at 0, 1, 2, 3 and 6 months.

[0034] Figure 3 : Comparison of novelty-suppressed food intake latency in rats of each group in the 0th experiment.

[0035] Figure 4 :Comparison of novelty-suppressed food intake latency in rats of each group in the 21st experiment.

[0036] Figure 5 : Comparison of novelty-suppressed food intake latency in rats of each group in the 35th experiment.

[0037] Figure 6 : Comparison of D-lactic acid content in rats of each experimental group.

[0038] Figure 7 : Comparison of D-lactic acid and TNF-α levels in serum of rats in each experimental group.

[0039] Figure 8 : Comparison of D-lactic acid and serum IL-6 levels in rats of each experimental group.

[0040] Figure 9 : Comparison of D-lactic acid and IFN-γ levels in serum of rats in each experimental group. DETAILED DESCRIPTION

[0041] It is particularly important to note that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be encompassed by the present invention. The methods and applications of the present invention have been described through the use of several embodiments. It is obvious that relevant persons can modify or appropriately change and combine the methods and applications described herein to implement and apply the technology of the present invention without departing from the content, spirit, and scope of the present invention.

[0042] Example 1: A Pinaverium Bromide Tablet and Its Preparation Method

[0043] Pinaverium bromide 10g, Rosa laevigata extract 0.5g, sodium carboxymethyl starch 2g, magnesium stearate 0.1g, microcrystalline cellulose 20g, lactose 20g.

[0044] Preparation process:

[0045] 1) Dissolve glyceryl monostearate in a mixed solution of chloroform and 95% or more ethanol, stirring continuously to mix thoroughly; wherein, calculated in g / mL, the weight-to-volume ratio of glyceryl monostearate is 1:100, and the volume ratio of chloroform to ethanol is 2:1; the amount of glyceryl monostearate used is 0.5 g.

[0046] 2) adding pinaverium bromide to step 1) and mixing, stirring to dissolve;

[0047] 3) adding the Rosa laevigata extract evenly to the mixed solution of step 2), maintaining the temperature at 40° C. and rotary evaporating under reduced pressure to dryness, adding microcrystalline cellulose, lactose, and sodium carboxymethyl starch, blending, sieving, adding magnesium stearate, and tableting to obtain plain tablets;

[0048] 4) Weigh 5 g of coating premix powder and add 20 g of water to mix to prepare a film coating premix, and film coat the plain tablets from step (3) to a coating weight gain of 3% (the remaining coating solution is recycled), followed by drying. Set the material temperature to 35° C. and continue drying until the free moisture content is below 3% to obtain tablets containing pinaverium bromide.

[0049] Example 2: A Pinaverium Bromide Tablet and Its Preparation Method

[0050] Pinaverium bromide 10g, Rosa laevigata extract 1.5g, sodium carboxymethyl starch 10g, magnesium stearate 1.1g, microcrystalline cellulose 60g, lactose 70g.

[0051] Preparation process:

[0052] 1) Dissolve glyceryl monostearate in a mixed solution of chloroform and 95% or greater ethanol, stirring continuously to mix thoroughly; calculated in g / mL, the weight-to-volume ratio of glyceryl monostearate is 1:100, and the volume ratio of chloroform to ethanol is 2:1; the amount of glyceryl monostearate used is 1.5 g.

[0053] 2) adding pinaverium bromide to step 1) and mixing, stirring to dissolve;

[0054] 3) adding the Rosa laevigata extract evenly to the mixed solution of step 2), maintaining the temperature at 40-50° C. and rotary evaporating under reduced pressure to dryness, adding microcrystalline cellulose, lactose, and sodium carboxymethyl starch, blending, sieving, adding magnesium stearate, and tableting to obtain plain tablets;

[0055] 4) Weigh 5 g of coating premix powder and add 20 g of water to mix to prepare a film coating premix, and film coat the plain tablets from step (3) to a coating weight gain of 10% (the remaining coating solution is recycled), followed by drying. Set the material temperature to 35° C. and continue drying until the free moisture is below 3%, thereby obtaining tablets containing pinaverium bromide.

[0056] Example 3: A Pinaverium Bromide Tablet and Its Preparation Method

[0057] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0058] Preparation process:

[0059] 1) Dissolve glyceryl monostearate in a mixed solution of chloroform and 95% or more ethanol, stirring continuously to mix thoroughly; wherein, calculated in g / mL, the weight-to-volume ratio of glyceryl monostearate is 1:100, and the volume ratio of chloroform to ethanol is 2:1; the amount of glyceryl monostearate used is 1 g.

[0060] 2) adding pinaverium bromide to step 1) and mixing, stirring to dissolve;

[0061] 3) adding the Rosa laevigata extract evenly to the mixed solution of step 2), maintaining the temperature at 40-50° C. and rotary evaporating under reduced pressure to dryness, adding microcrystalline cellulose, lactose, and sodium carboxymethyl starch, blending, sieving, adding magnesium stearate, and tableting to obtain plain tablets;

[0062] 4) Weigh 10 g of the coating premix powder and add 40 g of water to mix to prepare a film coating premix. The plain tablets from step (3) are film coated to a weight gain of 6% (the remaining coating solution is recycled). The mixture is then dried at a temperature of 35° C. and dried until the free moisture content is below 2% to obtain tablets containing pinaverium bromide.

[0063] Example 4: A Pinaverium Bromide Tablet and Its Preparation Method

[0064] Pinaverium bromide 10g, Rosa laevigata extract 1g, low-substituted hydroxypropyl cellulose 3g, talc 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0065] The preparation process is the same as that in Example 3.

[0066] Example 5: A Pinaverium Bromide Tablet and Its Preparation Method

[0067] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, micropowdered silica magnesium 0.6g, microcrystalline cellulose 40g, mannitol 45g.

[0068] The preparation process is the same as that in Example 3.

[0069] Example 6: A Pinaverium Bromide Tablet and Its Preparation Method

[0070] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, micronized silica magnesium 0.6g, sorbitol 40g, lactose 45g.

[0071] The preparation process is the same as that in Example 3.

[0072] Comparative Example 1: A Pinaverium Bromide Tablet and Its Preparation Method

[0073] Pinaverium bromide 10g, sodium starch glycolate 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0074] The preparation process is the same as that in Example 3.

[0075] Comparative Example 2: A Pinaverium Bromide Tablet and Its Preparation Method

[0076] Pinaverium bromide 10g, Rosa laevigata extract 2g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0077] The preparation process is the same as that in Example 3.

[0078] Comparative Example 3: A Pinaverium Bromide Tablet and Its Preparation Method

[0079] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 85g.

[0080] The preparation process is the same as that in Example 3.

[0081] Comparative Example 4: A Pinaverium Bromide Tablet and Its Preparation Method

[0082] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, sucrose 45g.

[0083] The preparation process is the same as that in Example 3.

[0084] Comparative Example 5: A Pinaverium Bromide Tablet and Its Preparation Method

[0085] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0086] Preparation process:

[0087] Pinaverium bromide and Rosa laevigata extract are added to a mixed solution of ethanol with a concentration of more than 95%, and the mixture is stirred continuously to mix evenly; the temperature is maintained at 40-50°C and the mixture is rotary evaporated to dryness under reduced pressure; microcrystalline cellulose, lactose, and sodium carboxymethyl starch are added and blended, the mixture is sieved, magnesium stearate is added, and the mixture is compressed to obtain plain tablets; 10 mg of coating premix powder is weighed and added to 40 mg of water to prepare a film coating premix, the plain tablets are film-coated, and the mixture is dried; the material temperature is set at 35°C, and the drying is continued until the free moisture is below 3%, thereby obtaining tablets containing pinaverium bromide.

[0088] Comparative Example 6: A Pinaverium Bromide Tablet and Its Preparation Method

[0089] Pinaverium bromide 10g, Panax notoginseng polysaccharide 1g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0090] Verification Example 1: Dissolution of Pinaverium Bromide Tablets and Determination of the Content of Related Substances

[0091] 1.1 Dissolution test and results of pinaverium bromide tablets

[0092] This experimental example investigates the dissolution changes of commercially available pinaverium bromide tablets (Beijing Fuyuan Pharmaceutical Co., Ltd., batch number national medicine standard H20133036), Examples 1-6, and Comparative Examples 1-6 containing pinaverium bromide tablets under pH 1.0 HCl solution conditions.

[0093] Specific dissolution determination method: pH 1.0 HCl solution is used as the medium and the dissolution is carried out at a speed of 50 rpm / min. The detection is carried out by ultraviolet spectrophotometry with a detection wavelength of 243 nm (based on pinaverium bromide). The test results are shown in Figure 1 .

[0094] According to the conventional requirements of tablets, the dissolution rate should be above 80% within 15 minutes. Figure 1 It can be seen that the dissolution rates of Examples 1-5 in the HCl solution at pH 1.0 at 0, 1, 2, 3, and 6 months of the accelerated test were above 99%, and the tablets containing pinaverium bromide prepared in Examples 1-5 all met the dissolution requirements of the Chinese Pharmacopoeia. However, in the accelerated test, the dissolution rates of Comparative Examples 1, 3, 4, 5, and 6 at 15 minutes were all lower than 85%, and Comparative Examples 3-5 were already lower than 80%, which failed to meet the requirements of the Pharmacopoeia.

[0095] 1.2 Determination of related substances in pinaverium bromide tablets and results

[0096] Determination of related substances: Determined by high performance liquid chromatography, with reference to the 2020 edition of the Chinese Pharmacopoeia

[0097] Chromatographic conditions: Octadecylsilane bonded silica gel as the filler, acetonitrile-sodium dodecyl sulfate buffer (70:30) as the mobile phase, detection wavelength at 245 nm, column temperature at 25°C, flow rate at 1.0 mL / min, injection volume at 20 μL. Preparation of sodium dodecyl sulfate buffer: Dissolve 13.0 g of sodium dodecyl sulfate in 1500 mL of water, then add 5.0 mL of phosphoric acid, mix thoroughly, adjust the pH to 2.5 with triethylamine, and filter.

[0098] Depend on Figure 2 As can be seen, compared with Comparative Examples 1-6, the total impurity content of the tablets of Examples 1-6 of the present invention in the accelerated test is substantially unchanged, while the total impurity content of Comparative Examples 1, 2, 3, and 5 significantly increases, showing that the stability of the tablet containing pinaverium bromide prepared using the inventive method is significantly improved, wherein the stability of Example 3 is the best. Comparative Example 1 does not contain Rosa Laevigata extract, and extract is particularly important for the stability of pinaverium bromide, and the inventors believe that polysaccharides can form a protective film on the drug surface. This film can isolate the contact of drug molecules with the external environment, slow down the impact of moisture, oxygen and light on pinaverium bromide, thereby reduce or avoid the rate of hydrolysis reaction, thereby improve the stability of the drug. The Rosa Laevigata extract of Comparative Example 2 is too high, and other substances inside may react with pinaverium bromide to cause degradation, and the different adjuvants employed in Comparative Example 3 also have an impact on the final product, and Comparative Example 5 has adopted different preparation processes, and the difference in preparation process is also available for the impact of pinaverium bromide, and pinaverium bromide is relatively sensitive to light and temperature, and does not take relevant means to accelerate its degradation.

[0099] Verification Example 2: Pharmacological Experiment on Rats of the Composition Tablets of the Present Invention

[0100] 2.1 Modeling and grouping

[0101] 2.1.1 Modeling

[0102] Seventy-two SPF female Wistar rats were adaptively raised for one week. Eight rats were randomly selected as the blank group using a random number table. The remaining rats were treated with a combined modeling method of intestinal perfusion of acetic acid, tail clamp stress, and mold restriction to establish a diarrhea-predominant irritable bowel syndrome model.

[0103] From days 1 to 14, all rats were fasted for 12 hours before enema administration. Anesthetized with 50 mg / kg of 3% sodium pentobarbital intraperitoneally at 8:30 AM daily. After anesthesia, an 8F paraffin-lubricated catheter was inserted 8 cm through the anus. Model rats were injected with 1 mL of 4% acetic acid, held for 30 seconds, and then an equal volume of phosphate-buffered saline was injected. The control group received 1 mL of saline. From days 7 to 21, model rats were restrained in a mold for 1 hour at 3:00 PM daily, followed by a plastic clamp clamping the proximal 1 / 3 of the tail for 1 hour. The control group received no intervention. A significant increase in fecal water content was considered a successful model (a significant difference in fecal water content between the model and control groups, P < 0.01, indicated successful model establishment).

[0104] 2.1.2 Grouping

[0105] The rats were divided into 5 groups according to the random number table: model group, positive control group, Example 1-3 groups, and Comparative Example 1 group and Comparative Example 6 group, with 8 rats in each group, and a blank group with no treatment.

[0106] 2.3 Administration

[0107] The pinaverium bromide tablets prepared in each example and the positive control drug, calculated as pinaverium bromide, 50 mg of pinaverium bromide content was ground and dissolved in 25 mL of distilled water to prepare a 2.50 mg / mL suspension. The above examples and suspensions prepared as needed were stored in a 4°C refrigerator for later use and gavaged twice a day in the morning and evening; the positive control group and each example group were given 5.40 mL·kg of pinaverium bromide suspension. -1 ·d -1 (i.e. 13.50 mg kg -1 ), once a day by gavage; the blank group and the model group were given 10 mL·kg normal saline -1 ·d -1 The drug was administered orally for 14 consecutive days.

[0108] 2.4 Specimen collection and processing

[0109] After the last dose of each drug, rats were fasted for 24 h. After weighing their bodies, they were anesthetized with an intraperitoneal injection of 50 mg / kg of 3% sodium pentobarbital. Approximately 4 mL of blood was rapidly drawn from the heart and placed in equal amounts into red cranial tubes (dry vacuum tubes without additives) and purple cranial tubes (blood collection tubes containing ethylenediaminetetraacetic acid and its salts). The tubes were centrifuged at 2500 rpm for 10 min. Serum and plasma were aspirated with a pipette and aliquoted, then frozen at -80°C until further use. A 3-4 cm section of colon tissue, 6-7 cm from the anal verge, was cut open along the longitudinal axis and rinsed with saline. The intestinal mucosal morphology was observed, and a 1 cm section of colon was rapidly fixed in paraformaldehyde fixative and embedded in paraffin 24 h later. Another 1 cm section of colon was rapidly fixed in electron microscopy solution at room temperature in the dark and stored in a 4°C refrigerator 2 h later. The remaining tissue was stored at -80°C for subsequent experiments.

[0110] 2.5 Experimental testing indicators

[0111] 2.5.1 Novelty-induced food intake suppression experiment

[0112] Novelty-suppressed feeding experiments were conducted on days 0, 21, and 35. Rats were fasted for 24 hours before the experiment and placed in a 50 cm × 50 cm × 50 cm open-top plastic box with bedding placed on the bottom and the same diet. The latency for the rats to start eating was observed and calculated within 5 minutes. The criterion for the onset of feeding was the rats starting to chew the food.

[0113] 2.5.2 Elisa assay for the determination of D-lactic acid in plasma and TNF-α, IL-6, and IFN-γ in serum

[0114] According to the operating steps on the kit, complete sample addition, incubation-washing, enzyme addition-incubation-washing, color development-stopping, and OD value determination in sequence. Substitute the OD value of the sample into the linear regression equation of the standard curve (calculated based on the concentration of the standard and the OD value) to obtain the sample concentration × 5, which is the actual concentration of the sample.

[0115] 2.6 Results

[0116] 2.6.1 Comparison of novelty-suppressed food intake latency in rats of different groups

[0117] Before modeling, the novelty suppression of food intake latency of rats in each group was compared. On day 0, there was no statistically significant difference (P>0.05). Figure 3 At the end of modeling, compared with the blank group, the latency of novelty suppression of food intake in the modeling group rats was significantly prolonged (P<0.01), indicating that the modeling was successful; after treatment, on the 21st day, the latency of novelty suppression of food intake in the Example 1-3 groups was significantly shortened compared with the positive group, the comparative example 1 group and the comparative example 2 group (P<0.05 or P<0.01), see for details. Figure 4After treatment, on the 35th day, the novelty suppression feeding latency of rats in Example 1-3 groups was significantly shortened compared with the positive group, Comparative Example 1 group and Comparative Example 2 group (P<0.01). Figure 5 2.6.2 Comparison of D-lactic acid in rat plasma and TNF-α, IFN-γ, and IL-6 in serum

[0118] Compared with the blank group, the levels of D-lactic acid in the plasma and TNF-α, IFN-γ, and IL-6 in the serum of the rats in the model group were significantly increased (P < 0.05, P < 0.01). Compared with the model group and the pinaverium bromide group, the levels of D-lactic acid and TNF-α, IFN-γ, and IL-6 in the serum of the rats in Examples 1-3 were significantly decreased (P < 0.05, P < 0.01). Figure 6-9 . DETAILED DESCRIPTION

[0119] It is particularly important to note that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be encompassed by the present invention. The methods and applications of the present invention have been described through the use of several embodiments. It is obvious that relevant persons can modify or appropriately change and combine the methods and applications described herein to implement and apply the technology of the present invention without departing from the content, spirit, and scope of the present invention.

[0120] Example: Preparation of Rosa Laevigata Extract

[0121] Method 1: Preparation of Rosa Laevigata Extract

[0122] 1) Take 500g of Rosa laevigata fruit pulp powder, add 30% sodium chloride and soak for 30 minutes, then heat to 70°C to extract the medicinal liquid, and set aside the medicinal residue and the extract;

[0123] 2) Repeat step 1) with the medicinal residue and extract twice; combine the filtrates from the three extractions;

[0124] 3) collecting the filtrate from step 2), concentrating under reduced pressure at 50-60° C. to an alcohol content of 80%; standing at room temperature for 24 hours, centrifuging, and collecting the precipitate and supernatant to obtain the Rosa laevigata extract;

[0125] 4) The protein of the Rosa laevigata extract obtained in step 3) was removed by the Sevag method, centrifuged, and the supernatant was concentrated. The mixed Rosa laevigata extract was added with 95% ethanol in a volume ratio of 1:4, placed in a refrigerator (4°C), and allowed to stand for 24 hours overnight. The mixture was centrifuged at 4000 rpm for 15 minutes, and the precipitate was collected and dissolved in an appropriate amount of deionized water to obtain 243.23 g of Rosa laevigata extract.

[0126] Method 2: Preparation of Rosa Laevigata Extract

[0127] 1) Take 500g of Rosa laevigata fruit pulp powder, add 60% sodium chloride and soak for 50 minutes, then heat to 80°C to extract the medicinal liquid, and set aside the medicinal residue and the extract;

[0128] 2) Repeat step 1) with the medicinal residue and extract twice; combine the filtrates from the three extractions;

[0129] 3) collecting the filtrate from step 2), concentrating under reduced pressure at 50-60° C. to an alcohol content of 90%; standing at room temperature for 24 hours, centrifuging, and collecting the precipitate and supernatant to obtain the Rosa laevigata extract;

[0130] 4) The protein of the Rosa laevigata extract obtained in step 3) was removed by the Sevag method, centrifuged, and the supernatant was concentrated. The mixed Rosa laevigata extract was added with 95% ethanol in a volume ratio of 1:4, placed in a refrigerator (4°C), and allowed to stand for 24 hours overnight. The mixture was centrifuged at 4000 rpm for 15 minutes, and the precipitate was collected and dissolved in an appropriate amount of deionized water to obtain 239.67 g of Rosa laevigata extract.

[0131] Method 3: Preparation of Rosa Laevigata Extract

[0132] 1) Take 500g of Rosa laevigata fruit pulp powder, add 45% sodium chloride and soak for 40 minutes, then heat to 75°C to extract the medicinal liquid, and set aside the medicinal residue and the extract;

[0133] 2) Repeat step 1) with the medicinal residue and extract twice; combine the filtrates from the three extractions;

[0134] 3) collecting the filtrate from step 2), concentrating under reduced pressure at 50-60° C. to an alcohol content of 85%; standing at room temperature for 24 hours, centrifuging, and collecting the precipitate and supernatant to obtain the Rosa laevigata extract;

[0135] 4) The protein of the Rosa laevigata extract obtained in step 3) was removed by the Sevag method, centrifuged, and the supernatant was concentrated. The mixed Rosa laevigata extract was added with 95% ethanol in a volume ratio of 1:4, placed in a refrigerator (4°C), and allowed to stand for 24 hours overnight. The mixture was centrifuged at 4000 rpm for 15 minutes, and the precipitate was collected and dissolved in an appropriate amount of deionized water to obtain 251.88 g of Rosa laevigata extract.

[0136] Method 4: Preparation of Rosa Laevigata Extract

[0137] 1) Take 500 g of Rosa laevigata fruit pulp powder, soak it in water for 40 minutes, then heat it to 75°C to extract the medicinal liquid. The medicinal residue and the extract are set aside;

[0138] 2) Repeat step 1) with the medicinal residue and extract twice; combine the filtrates from the three extractions;

[0139] 3) collecting the filtrate from step 2), concentrating under reduced pressure at 50-60° C. to an alcohol content of 85%; standing at room temperature for 24 hours, centrifuging, and collecting the precipitate and supernatant to obtain the Rosa laevigata extract;

[0140] 4) The Rosa laevigata extract obtained in step 3) was deproteinized using the Sevag method, centrifuged, and the supernatant was concentrated. The mixed Rosa laevigata extract was added with 50% ethanol at a volume ratio of 1:7.6, placed in a refrigerator (4°C), and allowed to stand for 24 hours overnight. The mixture was centrifuged at 4000 rpm for 15 minutes, and the precipitate was collected and dissolved in an appropriate amount of deionized water to obtain 187.40 g of Rosa laevigata extract.

[0141] Example 1: A Pinaverium Bromide Tablet and Its Preparation Method

[0142] Pinaverium bromide 10g, Rosa laevigata extract 0.5g, sodium carboxymethyl starch 2g, magnesium stearate 0.1g, microcrystalline cellulose 20g, lactose 20g.

[0143] Preparation process:

[0144] 1) dissolving glyceryl monostearate in a mixed solution of chloroform and 95% or more ethanol, stirring continuously to mix thoroughly; wherein the weight-to-volume ratio of glyceryl monostearate is 1:100, and the volume ratio of chloroform to ethanol is 2:1;

[0145] 2) adding pinaverium bromide to step 1) and mixing, stirring to dissolve;

[0146] 3) Add the Rosa Laevigata extract evenly into the mixed solution of step 2) and keep the temperature at 40-50°C

[0147] The mixture was rotary evaporated to dryness under reduced pressure, microcrystalline cellulose, lactose, and sodium carboxymethyl starch were added and blended, sieved, magnesium stearate was added, and tablets were obtained;

[0148] 4) Weigh 10 mg of the coating premix powder and add 40 mg of water to prepare a film coating premix. Film-coat the plain tablets to a weight gain of 3-10%, then dry the tablets at a temperature of 35° C. and continue drying until the free moisture is below 3%, thereby producing tablets containing pinaverium bromide.

[0149] Example 2: A Pinaverium Bromide Tablet and Its Preparation Method

[0150] Pinaverium bromide 10g, Rosa laevigata extract 1.5g, sodium carboxymethyl starch 10g, magnesium stearate 1.1g, microcrystalline cellulose 60g, lactose 70g.

[0151] The preparation process is the same as that in Example 3.

[0152] Example 3: A Pinaverium Bromide Tablet and Its Preparation Method

[0153] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0154] The preparation process is the same as that in Example 3.

[0155] Example 4: A Pinaverium Bromide Tablet and Its Preparation Method

[0156] Pinaverium bromide 10g, Rosa laevigata extract 1g, low-substituted hydroxypropyl cellulose 3g, talc 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0157] The preparation process is the same as that in Example 3.

[0158] Example 5: A Pinaverium Bromide Tablet and Its Preparation Method

[0159] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, micropowdered silica magnesium 0.6g, microcrystalline cellulose 40g, mannitol 45g.

[0160] The preparation process is the same as that in Example 3.

[0161] Example 6: A Pinaverium Bromide Tablet and Its Preparation Method

[0162] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, micronized silica magnesium 0.6g, sorbitol 40g, lactose 45g.

[0163] The preparation process is the same as that in Example 3.

[0164] Comparative Example 1: A Pinaverium Bromide Tablet and Its Preparation Method

[0165] Pinaverium bromide 10g, sodium starch glycolate 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0166] The preparation process is the same as that in Example 3.

[0167] Comparative Example 2: A Pinaverium Bromide Tablet and Its Preparation Method

[0168] Pinaverium bromide 10g, Rosa laevigata extract 2g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0169] The preparation process is the same as that in Example 3.

[0170] Comparative Example 3: A Pinaverium Bromide Tablet and Its Preparation Method

[0171] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 85g.

[0172] The preparation process is the same as that in Example 3.

[0173] Comparative Example 4: A Pinaverium Bromide Tablet and Its Preparation Method

[0174] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, sucrose 45g.

[0175] The preparation process is the same as that in Example 3.

[0176] Comparative Example 5: A Pinaverium Bromide Tablet and Its Preparation Method

[0177] Pinaverium bromide 10g, Rosa laevigata extract 1g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0178] Preparation process:

[0179] Pinaverium bromide and Rosa laevigata extract are added to a mixed solution of ethanol with a concentration of more than 95%, and the mixture is stirred continuously to mix evenly; the temperature is maintained at 40-50°C and the mixture is rotary evaporated to dryness under reduced pressure; microcrystalline cellulose, lactose, and sodium carboxymethyl starch are added and blended, the mixture is sieved, magnesium stearate is added, and the mixture is compressed to obtain plain tablets; 10 mg of coating premix powder is weighed and added to 40 mg of water to prepare a film coating premix, the plain tablets are film-coated, and the mixture is dried; the material temperature is set at 35°C, and the drying is continued until the free moisture is below 3%, thereby obtaining tablets containing pinaverium bromide.

[0180] Comparative Example 6: A Pinaverium Bromide Tablet and Its Preparation Method

[0181] Pinaverium bromide 10g, Panax notoginseng polysaccharide 1g, sodium carboxymethyl starch 3g, magnesium stearate 0.6g, microcrystalline cellulose 40g, lactose 45g.

[0182] The preparation process is the same as that in Example 3.

[0183] 1) Dissolution of Pinaverium Bromide Tablets and Determination of Related Substances

[0184] 1.1 Dissolution test and results of pinaverium bromide tablets

[0185] This experimental example investigates the dissolution changes of commercially available pinaverium bromide tablets (Beijing Fuyuan Pharmaceutical Co., Ltd., batch number national medicine standard H20133036), Examples 1-6, and Comparative Examples 1-6 containing pinaverium bromide tablets under pH 1.0 HCl solution conditions.

[0186] Specific dissolution determination method: pH 1.0 HCl solution is used as the medium and the dissolution is carried out at a speed of 50 rpm / min. The detection is carried out by ultraviolet spectrophotometry with a detection wavelength of 243 nm (based on pinaverium bromide). The test results are shown in Figure 1 .

[0187] According to the conventional requirements of tablets, the dissolution rate should be above 80% within 15 minutes. Figure 1 It can be seen that the dissolution rates of Examples 1-5 in the HCl solution at pH 1.0 at 0, 1, 2, 3, and 6 months of the accelerated test were above 99%, and the tablets containing pinaverium bromide prepared in Examples 1-5 all met the dissolution requirements of the Chinese Pharmacopoeia. However, in the accelerated test, the dissolution rates of Comparative Examples 1, 3, 4, 5, and 6 at 15 minutes were all lower than 85%, and Comparative Examples 3-5 were already lower than 80%, which failed to meet the requirements of the Pharmacopoeia.

[0188] 1.2 Determination of related substances in pinaverium bromide tablets and results

[0189] Determination of related substances: Determined by high performance liquid chromatography, with reference to the 2020 edition of the Chinese Pharmacopoeia

[0190] Chromatographic conditions: Octadecylsilane bonded silica gel as the filler, acetonitrile-sodium dodecyl sulfate buffer (70:30) as the mobile phase, detection wavelength at 245 nm, column temperature at 25°C, flow rate at 1.0 mL / min, injection volume at 20 μL. Preparation of sodium dodecyl sulfate buffer: Dissolve 13.0 g of sodium dodecyl sulfate in 1500 mL of water, then add 5.0 mL of phosphoric acid, mix thoroughly, adjust the pH to 2.5 with triethylamine, and filter.

[0191] Depend on Figure 2 As can be seen, compared with Comparative Examples 1-6, the total impurity content of the tablets of Examples 1-6 of the present invention in the accelerated test is substantially unchanged, while the total impurity content of Comparative Examples 1, 2, 3, and 5 significantly increases, showing that the stability of the tablet containing pinaverium bromide prepared using the inventive method is significantly improved, wherein the stability of Example 3 is the best. Comparative Example 1 does not contain the Fructus Rosae Laevigatae extract, and the extract is particularly important for the stability of pinaverium bromide, and the inventors believe that polysaccharides can form a protective film on the drug surface. This film can isolate the contact of drug molecules with the external environment, slow down the impact of moisture, oxygen and light on pinaverium bromide, thereby reduce or avoid the rate of hydrolysis reaction, thereby improve the stability of the drug. The Fructus Rosae Laevigatae extract of Comparative Example 2 is too high, and other substances inside may react with pinaverium bromide to cause degradation, and the different adjuvants employed in Comparative Example 3 also have an impact on the final product, and Comparative Example 5 has adopted different preparation processes, and the difference in preparation process is also available for the impact of pinaverium bromide, and pinaverium bromide is relatively sensitive to light and temperature, and does not take relevant means to accelerate its degradation.

[0192] 2.1 Modeling and grouping

[0193] 2.1.1 Modeling

[0194] Seventy-two SPF female Wistar rats were adaptively raised for one week. Eight rats were randomly selected as the blank group using a random number table. The remaining rats were treated with a combined modeling method of intestinal perfusion of acetic acid, tail clamp stress, and mold restriction to establish a diarrhea-predominant irritable bowel syndrome model.

[0195] From days 1 to 14, all rats were fasted for 12 hours before enema administration. Anesthetized with 50 mg / kg of 3% sodium pentobarbital intraperitoneally at 8:30 AM daily. After anesthesia, an 8F paraffin-lubricated catheter was inserted 8 cm through the anus. Model rats were injected with 1 mL of 4% acetic acid, held for 30 seconds, and then an equal volume of phosphate-buffered saline was injected. The control group received 1 mL of saline. From days 7 to 21, model rats were restrained in a mold for 1 hour at 3:00 PM daily, followed by a plastic clamp clamping the proximal 1 / 3 of the tail for 1 hour. The control group received no intervention. A significant increase in fecal water content was considered a successful model (a significant difference in fecal water content between the model and control groups, P < 0.01, indicated successful model establishment).

[0196] 2.1.2 Grouping

[0197] The rats were divided into 5 groups according to the random number table: model group, positive control group, Example 1-3 groups, and Comparative Example 1 group and Comparative Example 6 group, with 8 rats in each group, and a blank group with no treatment.

[0198] 2.3 Administration

[0199] The pinaverium bromide tablets prepared in each example and the positive control drug, calculated as pinaverium bromide, 50 mg of pinaverium bromide content was ground and dissolved in 25 mL of distilled water to prepare a 2.50 mg / mL suspension. The above examples and suspensions prepared as needed were stored in a 4°C refrigerator for later use and gavaged twice a day in the morning and evening; the positive control group and each example group were given 5.40 mL·kg of pinaverium bromide suspension. -1 ·d -1 (i.e. 13.50 mg kg -1 ), once a day by gavage; the blank group and the model group were given 10 mL·kg normal saline -1 ·d -1 The drug was administered orally for 14 consecutive days.

[0200] 2.4 Specimen collection and processing

[0201] After the last dose of each drug, rats were fasted for 24 h. After weighing their bodies, they were anesthetized with an intraperitoneal injection of 50 mg / kg of 3% sodium pentobarbital. Approximately 4 mL of blood was rapidly drawn from the heart and placed in equal amounts into red cranial tubes (dry vacuum tubes without additives) and purple cranial tubes (blood collection tubes containing ethylenediaminetetraacetic acid and its salts). The tubes were centrifuged at 2500 rpm for 10 min. Serum and plasma were aspirated with a pipette and aliquoted, then frozen at -80°C until further use. A 3-4 cm section of colon tissue, 6-7 cm from the anal verge, was cut open along the longitudinal axis and rinsed with saline. The intestinal mucosal morphology was observed, and a 1 cm section of colon was rapidly fixed in paraformaldehyde fixative and embedded in paraffin 24 h later. Another 1 cm section of colon was rapidly fixed in electron microscopy solution at room temperature in the dark and stored in a 4°C refrigerator 2 h later. The remaining tissue was stored at -80°C for subsequent experiments.

[0202] 2.5 Experimental Results

[0203] 2.5.1 Behavioral experiment (novelty suppression of feeding experiment)

[0204] Novelty-suppressed feeding experiments were conducted on days 0, 21, and 35 of the experiment. Rats were fasted for 24 hours before the experiment and placed in a 50 cm × 40 cm × 30 cm open-top plastic box with bedding on the bottom. Several pellets of the same size, quantity, and orientation were placed in a fixed position. The latency for the rats to start eating was observed and calculated within 5 minutes. The criterion for the onset of feeding was the rats starting to chew the food.

[0205] 2.5.2 Elisa assay for the determination of D-lactic acid in plasma and TNF-α, IL-6, and IFN-γ in serum

[0206] According to the operating steps on the kit, complete sample addition, incubation-washing, enzyme addition-incubation-washing, color development-stopping, and OD value determination in sequence. Substitute the OD value of the sample into the linear regression equation of the standard curve (calculated based on the concentration of the standard and the OD value) to obtain the sample concentration × 5, which is the actual concentration of the sample.

[0207] 2.6 Results 2.6.1

[0209] Before modeling, the novelty suppression of food intake latency of rats in each group was compared. On day 0, there was no statistically significant difference (P>0.05). Figure 3 At the end of modeling, compared with the blank group, the latency of novelty suppression of food intake in the modeling group rats was significantly prolonged (P<0.01), indicating that the modeling was successful; after treatment, on the 21st day, the latency of novelty suppression of food intake in the Example 1-3 groups was significantly shortened compared with the positive group, the comparative example 1 group and the comparative example 2 group (P<0.05 or P<0.01), see for details. Figure 4After treatment, on the 35th day, the novelty suppression feeding latency of rats in Example 1-3 groups was significantly shortened compared with the positive group, Comparative Example 1 group and Comparative Example 2 group (P<0.01). Figure 5 . 2.6.2

[0211] Compared with the blank group, the levels of D-lactic acid in the plasma and TNF-α, IFN-γ, and IL-6 in the serum of the rats in the model group were significantly increased (P < 0.05, P < 0.01). Compared with the model group and the pinaverium bromide group, the levels of D-lactic acid and TNF-α, IFN-γ, and IL-6 in the serum of the rats in Examples 1-3 were significantly decreased (P < 0.05, P < 0.01). Figure 6-9 .

Claims

1. A tablet containing pinaverium bromide, characterized in that The pinaverium bromide tablet contains the following raw materials: 10 parts by weight of pinaverium bromide, 0.5-1.5 parts by weight of Rosa laevigata extract, 2-10 parts by weight of disintegrant, 0.1-1.1 parts by weight of lubricant, and 40-130 parts by weight of filler.

2. Pinaverium bromide tablet according to claim 1, characterized in that, The pinaverium bromide tablet contains the following raw materials: 10 parts by weight of pinaverium bromide, 1 part by weight of Rosa laevigata extract, 3 parts by weight of disintegrant, 0.6 parts by weight of lubricant, and 85 parts by weight of filler.

3. Pinaverium bromide tablet according to claim 1, characterized in that, The filler is selected from one or two of microcrystalline cellulose, lactose, mannitol, and starch; more preferably, the filler is selected from a combination of microcrystalline cellulose and lactose.

4. Pinaverium bromide tablet according to claim 3, characterized in that, Calculated by weight, the ratio of microcrystalline cellulose to lactose is 2-6:2-7; more preferably, the ratio of microcrystalline cellulose to lactose is 8:

9.

5. The Pinaverium Bromide tablet according to claim 1, wherein The disintegrant is selected from one of low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch, preferably sodium carboxymethyl starch; the lubricant is selected from any one of magnesium stearate, talc, and sodium lauryl sulfate, preferably magnesium stearate.

6. The Pinaverium Bromide tablet according to claim 1, wherein The pinaverium bromide tablet contains the following raw materials: 10 parts by weight of pinaverium bromide, 0.5-1.5 parts by weight of Rosa laevigata extract, 2-10 parts by weight of sodium carboxymethyl starch, 0.1-1.1 parts by weight of magnesium stearate, 20-60 parts by weight of microcrystalline cellulose, and 20-70 parts by weight of lactose.

7. The Pinaverium Bromide tablet according to claim 1, wherein The pinaverium bromide tablet contains the following raw materials: 10 parts by weight of pinaverium bromide, 1 part by weight of Rosa laevigata extract, 3 parts by weight of sodium carboxymethyl starch, 0.6 parts by weight of magnesium stearate, 40 parts by weight of microcrystalline cellulose, and 45 parts by weight of lactose.

8. The Pinaverium Bromide tablet according to claim 1, wherein The pinaverium bromide tablets may be coated.

9. The Pinaverium bromide tablet according to any one of claims 1-2 or 6-7, characterized in that The extraction method of the Rosa laevigata extract is: 1) Take the Rosa laevigata fruit pulp powder, add 30-60% sodium chloride and soak for 30-50 minutes, then heat to 70-80°C to extract the medicinal liquid, and set aside the medicinal residue and the extract; 2) Repeat step 1) with the medicinal residue and extract twice; combine the filtrates from the three extractions; 3) collecting the filtrate from step 2), concentrating under reduced pressure at 50-60° C. to an alcohol content of 80-90%; standing at room temperature for 24 hours, centrifuging, and collecting the precipitate and supernatant to obtain the Rosa laevigata extract; 4) Deproteinizing the polysaccharide extract obtained in step 3) by the Sevag method, centrifuging, concentrating the supernatant, precipitating with ethanol, collecting the precipitate, and vacuum drying to obtain a Rosa laevigata extract.

10. The Pinaverium bromide tablet according to claim 8, characterized in that The preparation method of the pinaverium bromide tablets: 1) Dissolve glyceryl monostearate in a mixture of chloroform and 95% or more ethanol, stirring continuously to mix thoroughly; 2) adding pinaverium bromide to step 1) and mixing, stirring to dissolve; 3) adding the Rosa laevigata extract evenly to the mixed solution of step 2), maintaining the temperature at 40-50° C. and rotary evaporating under reduced pressure to dryness, adding microcrystalline cellulose, lactose, and sodium carboxymethyl starch, blending, sieving, adding magnesium stearate, and tableting to obtain plain tablets; 4) Weighing the coating premix powder and adding water to mix to prepare a film coating premix, film coating the above plain tablets to a coating weight gain of 3-10%, and drying to prepare tablets containing pinaverium bromide.

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