CN100381136C - A kind of pharmaceutical composition for treating constipation and its preparation and preparation method - Google Patents

Abstract

The invention discloses a pharmaceutical composition for treating constipation and its preparation and preparation method. The pharmaceutical composition is composed of plants of the genus Plantago and functional oligosaccharides, and the pharmaceutical composition of the invention is made into a solid preparation for oral administration The pharmaceutical composition of the present invention has better curative effect and low side effects, and the constipation symptom will not recur within a long period of time after the drug is stopped.

Description

A kind of pharmaceutical composition for treating constipation and its preparation and preparation method

technical field

The invention relates to a pharmaceutical composition for treating constipation, its formulation and preparation method, in particular to a pharmaceutical composition composed of plants of the genus Plantago and functional oligosaccharides, its preparation and preparation method.

Background technique

Constipation is one of the common clinical symptoms. A survey shows that 10% of the population suffers from this disease, and its incidence increases with age. Patients with constipation also increase the risk of colon cancer, especially the elderly often have heart and cerebrovascular diseases. disease, which is even more dangerous if accompanied by constipation.

At present, the medicines for clinically treating constipation can be roughly divided into three categories, mainly stimulant laxatives (such as rhubarb, senna, phenolphthalein, etc.), lubricating laxatives (such as glycerin) and volumetric laxatives (such as psyllium).

Among them, stimulant laxatives stimulate the intestinal mucosa and nerve plexus in the intestinal wall. Continuous application can cause water and electrolyte balance disorders, cause protein and vitamin absorption disorders, and also cause large intestine muscle weakness, easy to form dependence and fecal incontinence, etc.;

Lubricating laxatives are mostly inorganic mineral oils, which can prevent the absorption of intestinal water and easily pass through the intestinal cavity to soften the stool after use, but their effect is weak and cannot achieve effective therapeutic purposes. If these drugs are used for a long time, they will affect the function of fat-soluble vitamins. Absorption can also cause anal itching and osteomalacia;

Bulk laxatives are mainly non-digestible cellulose. This drug can increase the volume of feces, reduce the intestinal transit time, and will not over-stimulate the intestinal mucosa, which is in line with physiological conditions. Solvent-based drugs have the characteristics of less irritation and less side effects. Therefore, it is widely used in clinical practice.

Although volumetric drugs have the characteristics of few side effects in the treatment of constipation, volumetric drugs, like the other two types of drugs, generally have the disadvantage of being prone to recurrence after drug withdrawal, and can only temporarily relieve the symptoms of constipation.

Plantain, also known as plantago, wheel dish, pig ear grass, money string grass, etc., is Plantago asiatica L., P.L., P. depressa W.), Semen Plantago is the seeds of the above three plants (recorded in Part 1 of Chinese Pharmacopoeia 2000 Edition), and Plantago is used as medicine with the whole herb or seeds or seed husks of Plantago.

Plantago plant is the first-selected medicine as the volumetric medicine for treating constipation. When taking Plantago plant medicine alone to treat constipation, although the side effects are small, it can only temporarily relieve constipation symptoms. Relieves symptoms of constipation.

Therefore, the development of a drug that can not only effectively relieve the symptoms of constipation but also fundamentally treat constipation has become the current research direction in this field.

Contents of the invention

Aiming at the above technical defects, the present invention provides a new pharmaceutical composition for treating constipation.

The pharmaceutical composition of the present invention consists of plants of the genus Plantago and functional oligosaccharides.

Wherein the Plantago plant of the present invention can be any Plantago plant or their mixture which has the effect of treating constipation;

In the pharmaceutical composition of the present invention, the plants of the genus Plantago are preferably Plantago, Plantago, Plantain or Plantain or a mixture of two or more thereof;

The present invention preferably adopts the whole grass, seeds, seed husks or plant extracts of plants of the genus Plantago; Plant extract, the present invention is more preferably psyllium seed or seed hull.

The whole grass, seeds or seed shells of the Plantago plant used in the present invention should meet the requirements of the relevant national standards or industry standards for the plant.

When using the plant extract of the genus Plantago of the present invention as medicine, the extract is psyllium seed gum extracted from the plant of the genus Plantago, and its standard should also meet the requirements of relevant national standards or industry standards.

The Plantago plant extract of the present invention can be prepared by conventional extraction methods in the field, or can be purchased from the market and meet the relevant standards of the Plantago plant extract.

Plants of the genus Plantago can be used to treat constipation, mainly because the gum in the plants of the genus Plantago can absorb water after entering the intestinal tract and increase its volume, which plays a role in relaxing the bowels; in addition, the plants of the genus Plantago are also rich in The soluble fiber can combine with water to expand in the intestinal cavity, increase the volume of the intestinal content, stimulate the intestinal wall to speed up the flow of the intestinal content, reduce water absorption, soften the stool, and insoluble fiber forms a stool mass to be discharged. Thereby relieving constipation and improving constipation symptoms, but since patients with constipation are often accompanied by intestinal flora imbalance, using psyllium seed alone to treat constipation cannot fundamentally improve the intestinal environment, and the purpose of treating both symptoms and root causes cannot be achieved, and the drug should be discontinued Afterwards, it is easy to repeat, and excessive use can easily cause adverse reactions such as abdominal pain and abdominal distension. In addition, because the unilateral oral preparation of Plantaginaceae has a slightly bitter taste and poor mouthfeel, it can not better meet the needs of constipation patients who need medication.

In the pharmaceutical composition of the present invention, the functional oligosaccharides are preferably stachyose, raffinose, palatinose, lactulose, fructo-oligosaccharides, xylo-oligosaccharides, galacto-oligosaccharides, lactulose-oligosaccharides, Polyisomaltose, palatinose oligosaccharide or gentiooligosaccharide; it can also be a combination of two or more of them;

The functional oligosaccharide of the present invention is further preferably fructooligosaccharide or stachyose.

Since the occurrence of constipation is mostly related to intestinal function and intestinal flora imbalance, and bifidobacteria are important beneficial flora in the intestinal tract. However, there is no enzyme system for hydrolyzing functional oligosaccharides in the human body, so the functional oligosaccharides of the present invention are difficult or not digested and absorbed by the human body. The functional oligosaccharides directly enter the large intestine of the human body and are absorbed by the beneficial flora Rapid and selective absorption of bifidobacteria, rapid proliferation of bifidobacteria, and production of short-chain fatty acids, making the pH of the intestinal tract more acidic, inhibiting the growth of harmful bacteria, reducing the activity of certain harmful reductases, and reducing intestinal cancer The formation and accumulation of harmful metabolites and harmful metabolites really play a role in removing intestinal garbage, thereby playing a two-way regulation of the intestinal tract. In this way, the composition of the present invention not only relieves the symptoms of constipation, but also regulates the internal environment of the intestinal tract. , to ensure the balance of beneficial bacteria in the intestines, so that constipation is not easy to relapse after drug withdrawal, which just makes up for the defects of using volumetric drugs psyllium alone;

At the same time, functional oligosaccharides, as a good water-soluble dietary fiber, can also promote the slow peristalsis of the intestinal tract, thereby helping to enhance the effect of the psyllium plant in treating constipation.

The fructooligosaccharides and stachyose in the functional oligosaccharides of the present invention can also promote the synthesis of vitamins, especially the natural formation of vitamins B ₁ , B ₂ , B ₃ , B ₆ and folic acid in the human body, which improves the metabolism of the human body. Level, improve immunity and disease resistance, reduce the chance of human body suffering from constipation; at the same time, they can also enhance the absorption of calcium, magnesium, iron and other minerals, and promote growth and development.

Moreover, fructooligosaccharides and stachyose have pure sweetness, mellow taste, and unique fragrance, which just overcome the shortcomings of slightly bitter taste and poor taste in the unilateral oral preparation of psyllium seed, and meet the needs of constipation patients for medication.

In order to achieve the best preventive and therapeutic effects of the pharmaceutical composition of the present invention, the present inventors screened the proportions of the components in the composition of the present invention by using conventional screening techniques in the art.

The content of Plantago in the pharmaceutical composition of the present invention is preferably 10-40% (percentage by weight), and the content of functional oligosaccharides is preferably 60-90% (percentage by weight);

The ratio of each component in the pharmaceutical composition of the present invention is further preferably: the content of Plantago is 15-25% (weight percent), and the content of functional oligosaccharides is 75-85% (weight percent);

The optimal ratio of each component in the pharmaceutical composition of the present invention is: the content of Plantago is 17% (percentage by weight), and the content of functional oligosaccharides is 83% (percentage by weight);

The pharmaceutical composition of the present invention is mainly administered through the oral administration route, and the pharmaceutical composition of the present invention can be prepared into different solid preparations with common solid preparation pharmaceutical excipients in the art for administration, such as granules, capsules or Dosage forms such as tablets.

The dosage form of the pharmaceutical composition of the present invention is preferably a tablet, and the tablet of the pharmaceutical composition of the present invention is preferably obtained by the following methods:

1) Dry the plants of the genus Plantago or their extracts, fructooligosaccharides and diluents separately, pulverize them, pass through a 100-mesh sieve, sterilize with ultraviolet light for 1-3 hours, and then mix and sieve;

2) Add an appropriate amount of ethanol solution of the binder Povidone K ₃₀ to 1) to prepare a soft material, sieve and granulate, dry, add an appropriate amount of lubricant, mix evenly and press into tablets.

Wherein the consumption of diluent is 1-10% (percentage by weight) of tablet weight; The consumption of lubricant is 0.3-3% (percentage by weight) of tablet weight

In the tablet preparation process of the present invention, the diluent is preferably methyl cellulose, ethyl cellulose, hydroxypropyl cellulose or carboxymethyl cellulose; the lubricant is magnesium stearate or glyceryl behenate.

In the present invention, the ethanol solution of povidone K ₃₀ is preferably 8%-12% concentration of povidone K ₃₀ ethanol solution, more preferably 10% concentration of povidone K ₃₀ ethanol solution.

The present inventor adopts conventional screening techniques and screening methods in the field to screen different types and concentrations of diluents, adhesives, lubricants, and in combination with the characteristics of the pharmaceutical composition of the present invention itself. The result shows: diluent is comparatively suitable for the pharmaceutical composition of the present invention with cellulose, particularly methyl cellulose; Lubricant is good selection with magnesium stearate or behenic acid glyceride, especially magnesium stearate can make Tablet weight difference is small when tableting, and the surface is smooth; 8%-12% concentration of povidone K ₃₀ ethanol solution is the best choice for the binder, especially 10% concentration of povidone K ₃₀ ethanol solution can make granulation Easy, uniform and complete particles, good compressibility.

The pharmaceutical composition of the present invention can not only alleviate the symptoms of constipation well, but also achieve the effect of no recurrence after drug withdrawal by regulating the intestinal function of the human body and the beneficial flora in the intestinal tract. In order to improve immunity and disease resistance, it reduces the chance of human body suffering from constipation.

Experiments also show that the pharmaceutical composition of the present invention not only has better curative effect but also has lower side effects than the volumetric medicine psyllium chinensis alone, and constipation symptoms will not occur in a long period of time after stopping the medicine.

The pharmaceutical composition of the invention can not only be used as a medicine to treat people with constipation symptoms, but also can be used as a functional food to prevent and maintain people with mild constipation symptoms or tendencies to the symptoms.

Detailed ways

The present invention is further illustrated by specific experimental examples and examples but is not limited thereto.

Example 1:

Dry psyllium seed powder and methylcellulose at 50°C for 3 hours, grind them finely, pass through a 100-mesh sieve, and expose them to ultraviolet light for 2 hours; dry fructooligosaccharides at 50°C for 2 hours, grind finely, Pass through a 100-mesh sieve; fully mix 15.5g of psyllium powder and 5g of methylcellulose, pass through a 90-mesh sieve, add 75.5g of fructooligosaccharides, mix well, and sieve. Use an appropriate amount of 10% povidone K ₃₀ ethanol solution as a binder to make a suitable soft material, granulate with a 20-mesh sieve, dry in an oven at 60°C for 2 hours, granulate, add 2.0g of magnesium stearate, mix well, and make a round shape Stamped sheet, after passing the inspection, packed.

Example 2:

Dry plantain seed powder and hydroxypropyl cellulose at 50°C for 3 hours, grind them finely, pass through a 100-mesh sieve, and expose them to ultraviolet light for 2 hours; dry stachyose at 50°C for 2 hours, grind finely, Pass through a 100-mesh sieve; fully mix 10g of psyllium seed powder and 5g of hydroxypropyl cellulose, pass through a 90-mesh sieve, add 80g of stachyose, mix well, and sieve. Use an appropriate amount of 8% povidone K ₃₀ ethanol solution as a binder to make a suitable soft material, granulate with a 20-mesh sieve, dry in an oven at 60°C for 2 hours, granulate, add 1.0g of magnesium stearate, mix well, and make a round shape Stamped sheet, after passing the inspection, packed.

Example 3

Dry psyllium gum and carboxymethyl cellulose at 50°C for 3 hours, grind them finely, pass through a 100-mesh sieve, and expose them to ultraviolet light for 2 hours; dry galactooligosaccharides at 50°C for 2 hours, grind them , through a 100-mesh sieve; fully mix 20g psyllium gum and 8g carboxymethyl cellulose, pass through a 90-mesh sieve, add 70g galacto-oligosaccharides, mix well, and sieve. Use an appropriate amount of 12% povidone K ₃₀ ethanol solution as a binder, make a suitable soft material, granulate with a 20-mesh sieve, dry in an oven at 60°C for 2 hours, granulate, add 1.0g magnesium stearate, mix well, and round Stamped sheet, after passing the inspection, packed.

Example 4

Dry plantain seed powder and methyl cellulose at 60°C for 3 hours, grind them finely, pass through a 90-mesh sieve, and expose them to ultraviolet light for 2 hours; dry xylo-oligosaccharides at 50°C for 2 hours, grind them finely , through a 90-mesh sieve; fully mix 15g of plantain seed powder and an appropriate amount of methylcellulose, pass through a 90-mesh sieve, add 78g of xylo-oligosaccharides, mix evenly, and sieve. Use 10% povidone K ₃₀ ethanol solution as binder, make suitable soft material, granulate with 18 mesh sieve, dry in oven at 60°C for 2 hours, granulate, add appropriate amount of magnesium stearate, mix well, and make capsules , After passing the inspection, pack.

Example 5

Dry the psyllium seed husk powder and ethyl cellulose at 60°C for 5 hours, grind them finely, pass through a 90-mesh sieve, and expose them to ultraviolet light for 2 hours; dry the stachyose at 50°C for 2 hours, grind them finely , through a 90-mesh sieve; fully mix 15g of psyllium seed husk powder and 5g of ethyl cellulose, pass through a 90-mesh sieve, add 78g of stachyose, mix well, and sieve. Use 12% povidone K ₃₀ ethanol solution as binder, make suitable soft material, granulate with 18 mesh sieve, dry in oven at 60°C for 2 hours, granulate, add 2g behenic acid glyceride, mix well, and make capsule Agent, after passing the inspection, packaged.

Example 6

Dry plantain whole grass powder and methyl cellulose at 60°C for 4 hours, grind them finely, pass through a 100-mesh sieve, and expose them to ultraviolet light for 2 hours; dry isomaltooligosaccharide at 60°C for 2 hours, grind Fine, pass through a 90-mesh sieve; fully mix 15g flat plantain whole herb powder and 8g grade A cellulose, pass through a 90-mesh sieve, add 75g isomaltooligosaccharide, mix well, and sieve; take an appropriate amount of 8% povidone K ₃₀ % ethanol solution as a binder, made of suitable soft materials, granulated with 18 mesh sieve, oven-dried at 60°C for 2 hours, granulated, added with 1g of magnesium stearate, mixed evenly, made into granules, passed the inspection, and packed.

Example 7

Dry plantain seed powder and methyl cellulose at 60°C for 4 hours, grind them finely, pass through a 100-mesh sieve, and expose them to ultraviolet light for 2 hours; dry fructooligosaccharides at 60°C for 4 hours, grind finely, pass 90 mesh sieve; fully mix 17.5g plantain seed powder and appropriate amount of grade A cellulose, cross 90 mesh sieve, add 75.5g fructooligosaccharides and mix evenly, sieve; make with appropriate amount of 10% povidone K ₃₀ ethanol solution Adhesive, made of suitable soft materials, granulated with 18-mesh sieve, dried in an oven at 60°C for 2 hours, granulated, added with appropriate amount of magnesium stearate, mixed evenly, made into granules, passed the inspection, and packed.

Example 8

Dry psyllium seed powder and methyl cellulose at 50°C for 3 hours, grind them finely, pass through a 100-mesh sieve, and expose them to ultraviolet light for 2 hours; dry fructooligosaccharides at 50°C for 2 hours, grind finely , through a 100-mesh sieve; fully mix 15.5g psyllium powder and 5g methylcellulose, pass through a 90-mesh sieve, add 75.5g fructooligosaccharides, mix well, and sieve. Use an appropriate amount of 10% povidone K ₃₀ ethanol solution as a binder to make a suitable soft material, granulate with a 20-mesh sieve, dry in an oven at 60°C for 2 hours, granulate, add 2.0g of magnesium stearate, mix well, and make a round shape Stamped sheet, after passing the inspection, packed.

Test example 1:

Influence of composition of the present invention, psyllium seed powder, and fructooligosaccharide on dry constipation in mice

Composition of the present invention (embodiment 1), psyllium seed powder, and fructooligosaccharide: provided by Shandong Provincial Natural Medicine Engineering Technology Research Center. Suspend in physiological saline containing 10% activated carbon before use. Clean-grade Kunming mice, half male and half male, 18-22 g, were provided by the Animal Experiment Center of Shandong Provincial Natural Medicine Engineering Technology Research Center. Certificate number: Ludongzhizi No. 200106003.

2 methods

表示，以组间t检验进行统计学处理。Mice are randomly divided into blank control group (equal volume normal saline), composition group (0.8g/kg), plantago powder A group (0.14g/kg), fructooligosaccharide A group (0.6g/kg) , psyllium powder group B (0.8g/kg), fructooligosaccharide group B (0.8g/kg), 10 rats in each group. Animals in each group were respectively made dry-constipation models according to the literature method, then the mice were fasted for 12 hours, and the animals in each group were given corresponding medicines respectively, and the first black stool (containing activated carbon) was observed and recorded after the administration. Time, total mass of feces within 4 hours after administration. for data

Indicates that statistical analysis was performed by the t-test between groups.

3 results:

The results are shown in Table 1: the first defecation time of the mice in the composition group was significantly shorter than that of the blank control group (P<0.001), and the total weight of feces was significantly heavier than that of the blank control group (P<0.001).

The first defecation time of the mice in the composition group was significantly shorter than that of the plantain seed powder A group and the fructooligosaccharide A group (P＜0.01), and the total mass of the feces was significantly heavier than that of the plantain seed powder A group and the fructooligosaccharide A group (P<0.01).

The first defecation time of the mice in the composition group was significantly shorter than that of the plantain seed powder B group and the fructooligosaccharide B group (P＜0.05), and the total mass of feces was significantly heavier than that of the plantain seed powder B group and the fructooligosaccharide B group (P<0.05).

Table 1 composition of the present invention, psyllium powder, fructooligosaccharides are on the influence of mouse experimental constipation (n=10, )

Compared with the blank control group ^* P<0.05, ^** P<0.01, ^*** P<0.001; compared with the plantain seed powder A group ^a P<0.05, ^aa P<0.01; compared with the plantain seed powder B group ^b P<0.05, ^bb P<0.01; compared with FOS A group ^A P<0.05, ^AA P<0.05; compared with FOS B group ^B P<0.05, ^BB P<0.05.

4 conclusions: the composition of the present invention is better than the Semen Plantaginis powder or fructo-oligosaccharide of single use same dose to the catharsis effect of experimental constipation in mice, suggesting that the Semen-Psyllium powder and fructo-oligosaccharide contained in the composition are effective in treating There is a positive synergy in constipation.

Test example 2: animal acute toxicity test data of the composition medicine of the present invention

1. Purpose of the test: observe the maximum dosage of the composition of the present invention (Example 1) administered by intragastric administration to rats.

2. Test substance: Provider: Shandong Provincial Natural Medicine Engineering Technology Research Center; name, abbreviation, or code name: the composition of the present invention; 2.3 Properties: yellowish brown to brown tablet, fragrant; preparation auxiliary material: the main ingredient of the tablet Excipients are fructooligosaccharide, methyl cellulose and magnesium stearate, all of which are pharmacopoeia standards; specifications, packaging and batch number; packaged in white glass bottle, 100 tablets/bottle, batch number: 030712. 2.6 Storage conditions: store in room temperature and shade. Indoor humidity; operating requirements: operate in accordance with SOP; registration procedure: register as required each time you take it, and return the remaining medicines; solvent: pure water.

3. Animals: species and gender: SD rats, grade two. 3.2 Animal age: 50-60 days; animal weight: 120-130g; animal source: provided by the Experimental Animal Center of Shandong Luye Pharmaceutical Co., Ltd.; animal qualification certificate number: Ludongzhizi 200106005; test system Selection instructions: According to the "Technical Requirements for New Drug Research of Traditional Chinese Medicine" ^[1] , rats are used as the test system; the test system marking procedure: 5 rats per cage, and the cage card is marked with the subject number, test product number, animal number, group Gender, gender and dose level; Quarantine situation: Quarantine for one week according to SOP requirements, and reject unqualified animals; Experimental conditions: The conditions of the laboratory and the breeding room are the same. The room temperature is 18~25℃, the humidity is 40~60%, the air is filtered, and the light is 12 hours. The feed was provided by the Animal Center of Shandong Province, free to eat and drink, and the drinking water bottle was changed once a day.

4 Basis for dose design

4.1 The tablet is configured so that the concentration of the suspension that can be administered into the stomach is 5.0 g/ml.

4.4 According to the "Technical Requirements for New Drug Research of Traditional Chinese Medicine", the maximum volume of rats administered by intragastric administration of acute toxicity is 3ml/rat, so the designed dosage is 10g/kg, the administration volume is 2ml/100g body weight, and the daily administration is 1 Second-rate.

5 Test methods and results

5.1 Grouping of animals: Take 40 healthy rats, half male and half male. They were randomly divided into two groups, normal saline control group and drug group, 20 rats in each group.

5.2 Administration method: Rats were fasted for 12 hours without food, and after weighing, they were intragastrically administered at a dose of 10g/kg and an administration volume of 2ml/100g. The control group was given normal saline in the same way.

5.2.4 Observation indicators: Closely observe the toxicity and death of the rats after administration. After 4 hours, observe once a day for 14 consecutive days. Weigh yourself once a week. Rats with poor general condition and significant weight loss or weight gain were dissected, and the lesions of major organs were observed with naked eyes. If no death of the rat was observed, the maximum dose was calculated.

5.2.5 Results: After administration of the composition of the present invention, no abnormal reaction was seen in the rats, the activities were normal, and the color of urine and stool did not change significantly. Within 14 days, the coat of the rats was bright, and the diet, activities and body weight were all compared with those of the control group. There was no significant difference between groups.

Conclusion: The maximum dosage of the composition of the present invention (Example 1) once orally administered to rats is 10 g/kg. It can be considered as a substantially non-toxic substance.

Claims (11)

1. A medicinal composition for treating constipation, characterized in that the pharmaceutical composition is made up of 10-40% Plantago and 60-90% functional oligosaccharides by weight, wherein Plantago The plant is psyllium, psyllium, flat psyllium or psyllium; the functional oligosaccharides are stachyose, raffinose, palatinose, lactulose, fructooligosaccharides, xylooligosaccharides, oligosaccharides Galactose, lactulose-oligosaccharides, isomalto-oligosaccharides, palatinose-oligosaccharides or gentio-oligosaccharides. 2. The pharmaceutical composition according to claim 1, characterized in that the functional oligosaccharide is fructooligosaccharide or stachyose. 3. The pharmaceutical composition according to claim 1, wherein the Plantago plant is the whole plant, seeds, seed shells and extracts thereof of Plantago, Plantago, Plantain or Plantain. 4. The pharmaceutical composition according to claim 1, characterized in that the pharmaceutical composition consists of 15-25% by weight of Plantago and 75-85% by weight of functional oligosaccharides. 5. The pharmaceutical composition according to claim 4, characterized in that the pharmaceutical composition is composed of 17% by weight of Plantago and 83% by weight of functional oligosaccharides. 6. The preparation of the pharmaceutical composition according to claim 1, characterized in that the dosage form of the pharmaceutical composition is tablet, capsule or granule. 7. according to the preparation of the described pharmaceutical composition of claim 6, it is characterized in that the tablet of above-mentioned pharmaceutical composition obtains by following method: 1) Dry the plants of the genus Plantago or their extracts, fructooligosaccharides and diluents separately, pulverize them, pass through a 100-mesh sieve, sterilize with ultraviolet light for 1-3 hours, and then mix and sieve; 2) Add an appropriate amount of the binder Povidone K ₃₀ ethanol solution to 1) to prepare a soft material, sieve, granulate, dry, add an appropriate amount of lubricant, mix evenly and press into tablets. 8. The preparation of the pharmaceutical composition according to claim 7, characterized in that the amount of the diluent used is 1-10% of the weight of the tablet; the amount of the lubricant used is 0.3-3% of the weight of the tablet. 9. according to the described pharmaceutical composition of claim 7 or 8, it is characterized in that diluent is methyl cellulose, ethyl cellulose, hydroxypropyl cellulose or carboxymethyl cellulose; Lubricant is magnesium stearate or behenic acid glycerides. 10. The pharmaceutical composition according to claim 9, characterized in that the binder is an ethanol solution of povidone K ₃₀ with a concentration of 8%-12%. 11. The pharmaceutical composition according to claim 10, characterized in that the binder is a 10% concentration of povidone K ₃₀ ethanol solution.