Tranexamic acid osmotic pump type controlled release tablet as well as preparation method and application thereof

Abstract

The invention provides a tranexamic acid osmotic pump type controlled release tablet. The tranexamic acid osmotic pump type controlled release tablet comprises a tablet core and an insoluble semi-permeable coating membrane containing drug release holes, wherein the tablet core adopts a release regulator, a penetration enhancer and a lubricant with selected components, and the insoluble semi-permeable coating film adopts a semi-permeable polymer film-forming material with selected components, a pore-foaming agent and a plasticizer. According to the tranexamic acid osmotic pump type controlled release tablet, the 12-hour cumulative release percentage content of the preparation reaches 50-90%, the 24-hour medicine cumulative release percentage can reach 90-100%, the dosage form is suitable for administration once or twice every day, compared with a common tablet, the tranexamic acid osmotic pump type controlled release tablet has the advantages that the relative bioavailability in an animal body is 80-120%, the Cmax is reduced, the Tmax is prolonged, and the tranexamic acid osmotic pump type controlled release tablet can be applied to the animal body. The AUC is close, and the slow-release effect is obvious.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and specifically provides an osmotic pump type controlled-release tablet of tranexamic acid, and further discloses a preparation method and application thereof. Background Art

[0002] Heavy menstrual bleeding (HMB) refers to the pathological phenomenon of menstruation lasting more than 7 days and / or menstrual volume exceeding 80 mL. It is a common symptom in women of childbearing age and perimenopause. About 30% of women of childbearing age worldwide suffer from heavy menstruation. Heavy menstruation is a serious social problem. Its causes include dysfunctional uterine bleeding and organic diseases. It can not only lead to severe anemia, but also affect patients' social activities, sexual life and mental health, seriously affecting their quality of life. At present, about 35% of patients with heavy menstruation will eventually choose surgical treatment. However, among all patients who choose hysterectomy due to heavy menstruation, nearly 50% of patients have normal pathological sections of uterine specimens after surgery. In clinical practice, these patients with heavy menstruation who cannot find the cause (except for heavy menstruation, no endocrine dysfunction or organic lesions were found after careful examination) are summarized as idiopathic heavy menstruation. Based on the risks and related complications of surgery, especially for young women with fertility requirements or near menopause, surgery is not the best choice. Appropriate drug treatment can significantly reduce the proportion of surgery.

[0003] Drug treatment has the advantages of being non-invasive and preserving fertility. Treatment methods include taking progestogens, antifibrinolytics or non-steroidal anti-inflammatory drugs. Among them, progestogens are currently the most commonly used drugs for treating menorrhagia. Studies have also confirmed that progestogens can be used as luteal phase replacement therapy to effectively reduce the menstrual volume of patients with anovulatory menorrhagia, but for patients with ovulatory menorrhagia, progestogens are only effective for 20% of patients. In Europe and other countries, tranexamic acid has been used as a first-line drug for patients with idiopathic (unexplained) menorrhagia, patients with menorrhagia who have recent fertility requirements or are unwilling to choose hormone therapy.

[0004] Tranexamic acid (TXA) is a synthetic antifibrinolytic drug that inhibits fibrin degradation and thus exerts a hemostatic effect. The mechanism of action of tranexamic acid is that in the presence of tranexamic acid, the lysine receptor binding site of the plasmin of fibrin is occupied by tranexamic acid, which prevents the binding with fibrin monomers, thereby stabilizing the matrix structure of fibrin. Tranexamic acid is used to treat HMB and improve symptoms associated with heavy menstrual bleeding. It is widely used in clinical practice for various bleeding conditions, including menorrhagia, traumatic bleeding, elective cesarean section, total knee replacement, coronary artery surgery, spinal deformity surgery, orthognathic surgery, transurethral prostatectomy, aneurysmal subarachnoid hemorrhage, etc. Studies have shown that women with menorrhagia usually take 650 mg of tranexamic acid tablets orally, three times a day, with a total daily dose of 3.9 g. However, this treatment can cause gastrointestinal adverse reactions, including nausea, vomiting, diarrhea, and cramps. According to research, these gastrointestinal adverse reactions are caused by large doses of tranexamic acid and / or the rapid release of tranexamic acid into the stomach after administration.

[0005] At present, tranexamic acid mainly contains common tablets, capsules, powder for injection, injection in domestic marketed dosage forms, is used for general hemostasis. As Chinese patent CN102525878A discloses a tranexamic acid sustained-release solid composition, with tranexamic acid as raw material, adds the hydrophilic gel sustained-release skeleton material of appropriate proportion, the preparation thus obtained can reach zero-order release in 3h, maintains stable blood drug concentration, but its ratio in solid composition is 7%-20%, and the in vitro release rate is too fast, and the release time is too short. As patent CN104414991 discloses a tranexamic acid sustained-release preparation, adopts tranexamic acid and insoluble sustained-release skeleton material to be granulated rear tableting or powder direct tableting to prepare solid preparation, the tablet obtained can reach the effect of slow release in 3h, still has the problem that the in vitro release rate is too fast, the release time is too short. For example, U.S. Patent US2010143468A1 discloses a modified-release oral dosage form comprising tranexamic acid and a sustained-release material. The modified-release material may be an excipient added to the coating material, or a controlled-release material added to the tablet core, such as a gel-forming or hydratable polymer. The in vitro release of tranexamic acid in this solution is about 70% in vitro cumulative release in 45 minutes and about 100% in 120 minutes. The dosage form is suitable for administration twice or three times a day, which reduces the side effects of the drug and improves the safety of administration. However, there are still problems such as too fast in vitro release rate, too short release time, and 3 times of administration being slightly too many. For example, U.S. Patent US20120135079A1 discloses a new tranexamic acid dosage form, comprising a tablet core consisting of tranexamic acid and a release-controlling material and a coating layer consisting of a coating agent that is insoluble in water but soluble in an aqueous medium with a pH lower than 5 and preferably a pH lower than 4. The pH dependence of the coating material is used to limit the release of tranexamic acid, so that tranexamic acid is minimally released in the oral cavity, thereby overcoming the bitter taste. In addition, the coating material is insoluble in water but soluble in an environment with a pH lower than 5 and preferably a pH lower than 4, and controls the active therapeutic release of tranexamic acid in the patient's stomach and upper gastrointestinal tract, thereby improving the problem of rapid release of ordinary tablets in the stomach. However, this product only controls the drug to start releasing in an environment with a pH lower than 5, and does not have a very prominent sustained-release effect. Its in vitro cumulative release in a pH 1.2 hydrochloric acid dissolution medium and an intestinal fluid biological dissolution medium for 150 minutes is not less than 95%. Similarly, the release time is too short and the number of administrations is too many.For example, patent US20090214644A1 discloses a sustained-release oral dosage form comprising tranexamic acid and a sustained-release material or a delayed-release oral dosage form comprising tranexamic acid and a delayed-release material. The product is suitable for administration two to three times a day, and the cumulative release of the preparation in an in vitro dissolution medium of pH 1.2 is less than 10% in 2 hours, and then the cumulative release in a dissolution medium of pH 6.8 is greater than 90% in 45 minutes, which can maintain or improve the therapeutic effect of tranexamic acid while minimizing or eliminating the adverse gastrointestinal side effects of oral tranexamic acid treatment in patients. However, the preparation does not have a sustained-release effect, and the drug release rate is too fast and the administration frequency is large.

[0006] In summary, most traditional tranexamic acid sustained-release solid preparations have the problems of too fast release rate and short effective duration, which is related to the property of tranexamic acid being easily soluble in water and highly hydrophilic. Therefore, how to control its release rate and reduce gastrointestinal adverse reactions so as to maintain steady-state blood drug concentration during menstruation has become a difficulty in the preparation of this drug.

[0007] Oral sustained-release and controlled-release preparations are a type of oral drug release system that achieves an ideal therapeutic effect by controlling the drug release rate. Osmotic pump tablets are a system characterized by zero-order drug release kinetics and mainly use osmotic pressure as the drug release power. They can prolong the administration time, reduce the number of administrations, and have a constant release rate within a certain period of time, reduce the peak and valley of blood drug concentration, thereby effectively reducing the frequency and degree of adverse drug reactions; and drug release is less affected by in vivo conditions (such as pH value, gastrointestinal motility, etc.), and has good in vitro and in vivo correlation, which greatly improves the safety and effectiveness of the drug. Therefore, in order to achieve the purpose of reducing the number of medications, reducing blood drug concentration fluctuations, and reducing side effects, the art expects to develop tranexamic acid osmotic pump controlled-release tablets for daily administration 1-2 times in combination with the characteristics of tranexamic acid to improve patients' medication compliance. However, tranexamic acid is also limited by its water-soluble and highly hydrophilic properties, and the large dose of tranexamic acid each time. Therefore, how to control its release rate under the premise of large doses so that it can maintain a steady-state blood drug concentration during menstruation has become a difficulty in this type of drug preparation. It is relatively difficult to control the release rate of tranexamic acid using an osmotic pump controlled-release system. Summary of the invention

[0008] To this end, the technical problem to be solved by the present invention is to provide an osmotic pump controlled-release tablet of tranexamic acid, so as to solve the problems of the conventional tranexamic acid sustained-release preparation in the prior art, such as the high number of administration times and the large dosage, and the large gastrointestinal adverse reactions caused by the rapid release in the stomach;

[0009] The second technical problem to be solved by the present invention is to provide a preparation method and application of the above-mentioned osmotic pump type controlled-release tablets of tranexamic acid.

[0010] In order to solve the above technical problems, the present invention provides an osmotic pump controlled-release tablet of tranexamic acid, wherein the controlled-release tablet comprises a tablet core and an insoluble semipermeable coating membrane containing drug-releasing holes; wherein:

[0011] The tablet core comprises the following raw material components in terms of total weight: 60-90 wt % of tranexamic acid, 2-30 wt % of a penetration enhancer, 2-30 wt % of a release regulator, 0.1-3 wt % of a lubricant, and 0.1-4 wt % of a wetting agent;

[0012] The insoluble semipermeable coating film comprises the following raw material components in terms of weight: 90-100 wt % of semipermeable film-forming material, 0-10 wt % of pore-forming agent, and 0-10 wt % of plasticizer.

[0013] Preferably, the osmotic pump controlled-release tablet of tranexamic acid, the tablet core, calculated by total amount, comprises the following raw material ingredients in mass content: 70-85wt% of tranexamic acid, 7-22wt% of penetration enhancer, 3-15wt% of release regulator, 1-2wt% of lubricant, and 1-2wt% of wetting agent.

[0014] Preferably, the osmotic pump controlled-release tablets of tranexamic acid, the tablet core, calculated by total amount, comprises the following raw material and auxiliary material components in weight: 71.94-84.03wt% of tranexamic acid, 7.46-21.58wt% of penetration enhancer, 3.60-14.93wt% of release regulator, 1.44-1.68wt% of lubricant, and 1.44-1.68wt% of wetting agent.

[0015] Preferably, in the osmotic pump controlled-release tablets of tranexamic acid, the insoluble semipermeable coating film comprises, based on its total amount, the following raw material and auxiliary material components in weight: 95-100wt% of semipermeable film-forming material, 0-5wt% of pore-forming agent, and 0-5wt% of plasticizer.

[0016] Preferably, in the osmotic pump controlled-release tablets of tranexamic acid, the insoluble semipermeable coating film comprises, based on its total amount, the following raw material and auxiliary material components in weight: 100 wt % of semipermeable film-forming material.

[0017] Specifically, in the osmotic pump controlled-release tablets of tranexamic acid, in the tablet core, the release regulator includes one or a mixture of several of hydroxypropyl methylcellulose, hydroxyethyl cellulose, polyoxyethylene, hydroxypropyl cellulose, polyvinyl pyrrolidone, sodium alginate or guar gum.

[0018] Specifically, in the osmotic pump controlled-release tablets of tranexamic acid, in the tablet core, the penetration enhancer includes one or a mixture of several of sodium chloride, potassium chloride, glucose, sucrose, lactose, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, d-mannitol, urea, magnesium succinate, sorbitol or tartaric acid; preferably, the penetration enhancer includes one or a mixture of several of sodium chloride, glucose, mannitol or lactose.

[0019] Specifically, in the osmotic pump controlled-release tablets of tranexamic acid, in the tablet core, the lubricant includes one or a mixture of magnesium stearate, talc, colloidal silicon dioxide, sodium stearyl fumarate or magnesium lauryl sulfate.

[0020] Specifically, in the osmotic pump controlled-release tablets of tranexamic acid, in the tablet core, the wetting agent includes polyvinyl pyrrolidone and / or ethanol; preferably, the wetting agent includes PVP K30 aqueous solution, PVP K30 ethanol solution or anhydrous ethanol.

[0021] Specifically, in the osmotic pump controlled-release tablets of tranexamic acid, in the insoluble semipermeable coating film, the semipermeable film-forming material includes one or a mixture of cellulose acetate, ethyl cellulose or acrylic resin.

[0022] Specifically, in the osmotic pump controlled-release tablets of tranexamic acid, in the insoluble semipermeable coating film, the pore-forming agent includes one or a mixture of several of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene glycol, propylene glycol, water-soluble inorganic salts or polyvinyl pyrrolidone.

[0023] Specifically, in the osmotic pump controlled-release tablets of tranexamic acid, the plasticizer in the insoluble semipermeable coating film includes one or a mixture of glycerol, polyethylene glycol, triacetin, castor oil, acetylated monoglyceride or phthalate.

[0024] Preferably, the osmotic pump controlled-release tablet of tranexamic acid:

[0025] The tablet core comprises the following raw material and auxiliary material components in total amount: 71.94-84.03wt% of tranexamic acid, 7.46-21.58wt% of sodium chloride, 3.60-14.93wt% of polyvinyl pyrrolidone, 1.44-1.68wt% of magnesium stearate, and 1.44-1.68wt% of wetting agent; wherein the wetting agent is an aqueous solution prepared with a selected amount of polyvinyl pyrrolidone;

[0026] The insoluble semipermeable coating film comprises the following raw material components in terms of weight: 100 wt % of ethyl cellulose.

[0027] As a preferred embodiment, the osmotic pump controlled-release tablets of tranexamic acid, each of which comprises:

[0028] The tablet core comprises: 100 mg of tranexamic acid, 50 mg of PVP K30, 50 mg of sodium chloride, 10 mg of magnesium stearate, and 0.2 ml of 5% PVP K30 aqueous solution;

[0029] The insoluble semipermeable coating film comprises ethyl cellulose, and the weight gain of the insoluble semipermeable coating film is 10-20 wt %.

[0030] Specifically, in the osmotic pump controlled-release tablets of tranexamic acid, the mass ratio of the insoluble semipermeable coating film to the tablet core is 5-20:100, that is, the weight gain of the coating is controlled to be 5-20%.

[0031] Preferably, in the osmotic pump controlled-release tablets of tranexamic acid, the mass ratio of the insoluble semipermeable coating film to the tablet core is 10-20:100, that is, the weight gain of the coating is controlled to be 10-20%.

[0032] Specifically, in the osmotic pump controlled-release tablet of tranexamic acid, the drug-releasing holes are distributed on both sides of the insoluble semipermeable coating membrane;

[0033] Preferably, the diameter of the drug release hole is 0.4 mm-1.2 mm.

[0034] Specifically, the osmotic pump type controlled-release tablet of tranexamic acid is a tranexamic acid single-layer osmotic pump tablet preparation;

[0035] In the controlled-release tablet, the cumulative release percentage of tranexamic acid in 12 hours is 50-90%, and the cumulative release percentage of the drug in 24 hours is 80-100%. Zero-order release can be maintained within 12 hours without release lag, ensuring that the drug can take effect quickly while maintaining a stable blood drug concentration in the body, reducing toxic side effects.

[0036] The present invention also discloses an osmotic pump controlled-release tablet for preparing the tranexamic acid, which is characterized by comprising the following steps:

[0037] (1) taking selected amounts of the tranexamic acid, the penetration enhancer, and the release regulator, mixing them, adding the wetting agent to form a soft material, sieving and granulating, and drying, continuing to add the lubricant to mix, and pressing to obtain a single-layer osmotic pump tablet core;

[0038] (2) taking a selected amount of the semipermeable membrane-forming material, pore-forming agent and plasticizer, adding water and mixing to form a coating solution;

[0039] (3) coating the core tablet with the coating liquid to obtain the desired coated tablet, and forming the desired drug release holes on both sides of the coated tablet.

[0040] Specifically, in step (2), the concentration of the coating solution is controlled to be 5-30wt%.

[0041] Specifically, as an practicable manner, the method for preparing the coating solution includes: weighing a prescribed amount of a semipermeable membrane-forming material and a pore-forming agent, dissolving them in a prescribed amount of acetone and purified water, respectively, and mixing the two evenly to form a coating solution of a desired concentration; or, weighing a prescribed amount of a semipermeable membrane coating material suspension, a pore-forming agent and a plasticizer, and adding a prescribed amount of purified water to dilute them to a concentration suitable for coating.

[0042] Specifically, the step (3) further includes a step of subjecting the coated tablet to an aging treatment;

[0043] Preferably, the temperature of the aging treatment step is 30-50°C, and the aging treatment time is 10-15h;

[0044] Preferably, in step (3), the drug release holes are formed at the center positions of the circles on both sides of the coated tablet.

[0045] The invention also discloses the use of the osmotic pump type controlled-release tablet of tranexamic acid in preparing a medicine for treating menorrhagia, especially idiopathic menorrhagia.

[0046] The osmotic pump controlled-release tablet of tranexamic acid of the present invention comprises a tablet core and an insoluble semipermeable coating film containing drug release holes; wherein the tablet core adopts a release regulator, a penetration enhancer and a lubricant of selected components, and the insoluble semipermeable coating film adopts a semipermeable polymer film-forming material of selected components as well as a pore-forming agent and a plasticizer to form a desired osmotic pump controlled-release system. The osmotic pump controlled-release tablet of tranexamic acid of the present invention is a tranexamic acid monolayer osmotic pump tablet preparation, which is a type of oral drug release system that achieves an ideal therapeutic effect by controlling the drug release rate. The osmotic pump controlled-release tablet mainly uses osmotic pressure as the drug release power, is characterized by zero-order drug release kinetics, can effectively prolong the administration time, reduce the number of administrations, and maintain a constant release rate within a certain period of time, reduce the peak and valley of blood drug concentration, thereby reducing the frequency and degree of adverse drug reactions, especially the drug release of the tablet is less affected by in vivo conditions (such as pH value, gastrointestinal motility, etc.), has a good in vitro and in vivo correlation, and greatly improves the safety and effectiveness of the drug. The osmotic pump controlled-release tablets of tranexamic acid disclosed in the present invention effectively solve the technical problems of traditional sustained-release dosage forms, such as the large number of administration times and the large dosage, as well as the large gastrointestinal adverse reactions caused by the rapid release of the preparation in the stomach.

[0047] As a preferred solution, the osmotic pump controlled-release tablets of tranexamic acid of the present invention, the coating material used is an ethyl cellulose aqueous dispersion suspension, and the solvent is purified water, which avoids the use of the organic solvent acetone, and avoids acetone as an inflammable and easy-to-prepare organic solvent, has a special pungent smell, is volatile when used, has higher requirements for coating equipment, has higher costs, and pollutes the environment and requires a special gas treatment device. The ethyl cellulose aqueous dispersion suspension used in the osmotic pump controlled-release tablets of the present invention only requires the simplest coating device, and is not volatile, reducing the loss of the coating solution during use.

[0048] The osmotic pump controlled-release tablet of tranexamic acid of the present invention can release stably and at a constant rate. The cumulative release percentage of the preparation in 12 hours reaches 50-90%, and the cumulative release percentage of the drug in 24 hours can reach 90-100%. Only one dose is needed per day. Compared with ordinary tablets, the relative bioavailability of the tranexamic acid osmotic pump controlled-release tablet in animals is between 80% and 120%, Cmax is reduced, Tmax is prolonged, AUC is close, and the tablet has an obvious sustained-release effect. The osmotic pump type controlled-release tablet of tranexamic acid of the present invention has an osmotic pressure difference between the inside and outside of the semipermeable membrane as the main drug release power of the preparation, and the drug can maintain zero-order release within 12 hours without release time lag, thereby ensuring that the drug can take effect quickly while maintaining a stable blood drug concentration in the body, prolonging the effective time of the drug and reducing toxic side effects; in particular, the in vitro drug release degree of the osmotic pump type controlled-release tablet in the first two hours is less than 20%, indicating that the preparation is released slowly in the stomach, reducing gastrointestinal adverse reactions, and the drug release behavior of the preparation is not affected by physiological factors such as gastrointestinal motility, pH, gastric emptying time, etc., and the adverse reactions to the gastrointestinal tract are low, and the preparation has a good controlled release effect, and therefore has a good practical application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] In order to make the content of the present invention more clearly understood, the present invention is further described in detail below according to specific embodiments of the present invention in conjunction with the accompanying drawings, wherein:

[0050] Figure 1 The in vitro cumulative release percentage-time curve of the tranexamic acid monolayer osmotic pump controlled-release tablets prepared in Example 1;

[0051] Figure 2 The in vitro cumulative release percentage-time curve of the tranexamic acid monolayer osmotic pump controlled-release tablets prepared in Example 2;

[0052] Figure 3 The in vitro cumulative release percentage-time curve of the tranexamic acid monolayer osmotic pump controlled-release tablets prepared in Example 3;

[0053] Figure 4The in vitro cumulative release percentage-time curve of the tranexamic acid monolayer osmotic pump controlled-release tablets prepared in Example 4;

[0054] Figure 5 The in vitro cumulative release percentage-time curve of the tranexamic acid monolayer osmotic pump controlled-release tablets prepared in Example 5;

[0055] Figure 6 The in vitro cumulative release percentage-time curve of the tranexamic acid monolayer osmotic pump controlled-release tablets prepared in Example 6;

[0056] Figure 7 The in vitro cumulative release percentage-time curve of the tranexamic acid monolayer osmotic pump controlled-release tablets prepared for Comparative Example 1;

[0057] Figure 8 The average blood drug concentration-time curves of beagle dogs after oral administration of the reference preparation (ordinary tablets);

[0058] Fig. 9 The average blood drug concentration-time curves of beagle dogs after oral administration of the test preparations (osmotic pump controlled-release tablets);

[0059] Fig.10 The average blood drug concentration-time curves after oral administration of the reference preparation (ordinary tablets) and the test preparation (osmotic pump controlled-release tablets) to beagle dogs;

[0060] Fig.11 The fitting results of the in vitro cumulative release percentage-time curves of the tranexamic acid monolayer osmotic pump controlled-release tablets prepared for Example 4 and Comparative Example 1;

[0061] Fig.12 The fitting results of the in vitro cumulative release percentage-time curve of the tranexamic acid monolayer osmotic pump controlled release tablets prepared in Example 1-4;

[0062] Fig.13 The fitting results of the in vitro cumulative release percentage-time curve of the tranexamic acid monolayer osmotic pump controlled-release tablets prepared in Example 4-6. DETAILED DESCRIPTION

[0063] The present invention is further described by the following examples, but the present invention is not limited thereto.

[0064] In the following examples of the present invention, the names of the substances involved are shown in Table 1 below.

[0065] Table 1 Name of substances involved

[0066] Abbreviations English name Chinese name TXA Tranexamic acid Tranexamic acid HMB Heavy menstrual bleeding Heavy menstruation PVP-K30 Polyvinylpyrrolidone K30 Polyvinylpyrrolidone-K30 NaCl Sodium chloride Sodium chloride PEO WSR-N80 Polyoxyethylene Polyethylene oxide WSR-N80

[0067] Example 1

[0068] The present embodiment describes an osmotic pump controlled-release tablet of tranexamic acid, wherein the controlled-release tablet comprises a tablet core and an insoluble semipermeable coating membrane having drug-releasing holes; wherein:

[0069] The tablet core includes the following raw material ingredients (per tablet):

[0070]

[0071]

[0072] The insoluble semipermeable coating film comprises the following raw material ingredients (based on tablet weight per 100g):

[0073] 40 ml of 25% solid content ethyl cellulose suspension;

[0074] 26.7ml of purified water.

[0075] The preparation process of the tranexamic acid monolayer osmotic pump controlled-release tablets described in this embodiment comprises the following steps:

[0076] (1) Wet granulation: The selected amount of tranexamic acid and excipients PVP-K30 and NaCl are crushed and dispersed through an 80-mesh sieve, then mixed evenly, a 5% PVP K30 aqueous solution is added to moisten the soft material, granulated through a 20-mesh sieve, dried at 40° C., the moisture content is controlled to be less than 3%, granulated through a 20-mesh sieve, and the prescribed amount of magnesium stearate is added and mixed evenly; a single-layer osmotic pump tablet core is pressed using a circular shallow concave die with a diameter of 11.6 mm;

[0077] (2) Preparing a coating solution: weighing a prescribed amount of a semipermeable membrane coating material suspension, adding a prescribed amount of purified water to dilute it, and obtaining a coating solution;

[0078] (3) Coating: The tablet cores are coated with a coating solution, the coating weight gain is controlled to be 20%, and the coated products are aged at 40° C. for 12 h to obtain coated tablets; a drug release hole with a diameter of 0.4-1.2 mm is punched on the upper and lower sides of the coating film of the osmotic pump tablets using a laser.

[0079] Example 2

[0080] The present embodiment describes an osmotic pump controlled-release tablet of tranexamic acid, wherein the controlled-release tablet comprises a tablet core and an insoluble semipermeable coating membrane having drug-releasing holes; wherein:

[0081] The tablet core includes the following raw material ingredients (per tablet):

[0082]

[0083] The insoluble semipermeable coating film comprises the following raw material ingredients (based on tablet weight per 100g):

[0084] 80 ml of 25% solid content ethyl cellulose suspension;

[0085] 53.3ml of purified water.

[0086] The preparation process of the tranexamic acid monolayer osmotic pump controlled-release tablets described in this embodiment comprises the following steps:

[0087] (1) Wet granulation: The selected amount of tranexamic acid and excipients PVP-K30 and NaCl are crushed and dispersed through an 80-mesh sieve, then mixed evenly, a 5% PVP K30 aqueous solution is added to moisten the soft material, granulated through a 20-mesh sieve, dried at 40° C., the moisture content is controlled to be less than 3%, granulated through a 20-mesh sieve, and the prescribed amount of magnesium stearate is added and mixed evenly; a single-layer osmotic pump tablet core is pressed using a circular shallow concave die with a diameter of 11.6 mm;

[0088] (2) Preparing a coating solution: weighing a prescribed amount of a semipermeable membrane coating material suspension, adding a prescribed amount of purified water to dilute it, and obtaining a coating solution;

[0089] (3) Tablet pressing: The tablet cores are coated with a coating solution, the coating weight gain is controlled to be 15%, and the coated products are aged at 40° C. for 12 h to obtain coated tablets; a drug release hole with a diameter of 0.4-1.2 mm is punched on the upper and lower sides of the coating film of the osmotic pump tablets using a laser.

[0090] Example 3

[0091] The present embodiment describes an osmotic pump controlled-release tablet of tranexamic acid, wherein the controlled-release tablet comprises a tablet core and an insoluble semipermeable coating membrane having drug-releasing holes; wherein:

[0092] The tablet core includes the following raw material ingredients (per tablet):

[0093]

[0094] The insoluble semipermeable coating film comprises the following raw material ingredients (based on tablet weight per 100g):

[0095] 60 ml of 25% solid content ethyl cellulose suspension;

[0096] 40ml of purified water.

[0097] The preparation process of the tranexamic acid monolayer osmotic pump controlled-release tablets described in this embodiment comprises the following steps:

[0098] (1) Wet granulation: The selected amount of tranexamic acid and excipients PVP-K30 and NaCl are crushed and dispersed through an 80-mesh sieve, then mixed evenly, a 5% PVP K30 aqueous solution is added to moisten the soft material, granulated through a 20-mesh sieve, dried at 40° C., the moisture content is controlled to be less than 3%, granulated through a 20-mesh sieve, and the prescribed amount of magnesium stearate is added and mixed evenly; a single-layer osmotic pump tablet core is pressed using a circular shallow concave die with a diameter of 11.6 mm;

[0099] (2) Preparing a coating solution: weighing a prescribed amount of a semipermeable membrane coating material suspension, adding a prescribed amount of purified water to dilute it, and obtaining a coating solution;

[0100] (3) Coating: The tablet cores are coated with a coating solution, the coating weight gain is controlled to be 15%, and the coated products are aged at 40° C. for 12 h to obtain coated tablets; a drug release hole with a diameter of 0.4-1.2 mm is punched on the upper and lower sides of the coating film of the osmotic pump tablets using a laser.

[0101] Example 4

[0102] The present embodiment describes an osmotic pump controlled-release tablet of tranexamic acid, wherein the controlled-release tablet comprises a tablet core and an insoluble semipermeable coating membrane having drug-releasing holes; wherein:

[0103] The tablet core includes the following raw material ingredients (per tablet):

[0104]

[0105] The insoluble semipermeable coating film comprises the following raw material ingredients (based on tablet weight per 100g):

[0106] 60 ml of 25% solid content ethyl cellulose suspension;

[0107] 40ml of purified water.

[0108] The preparation process of the tranexamic acid monolayer osmotic pump controlled-release tablets described in this embodiment comprises the following steps:

[0109] (1) Wet granulation: The selected amount of tranexamic acid and excipients PVP-K30 and NaCl are crushed and dispersed through an 80-mesh sieve, then mixed evenly, a 5% PVP K30 aqueous solution is added to moisten the soft material, granulated through a 20-mesh sieve, dried at 40° C., the moisture content is controlled to be less than 3%, granulated through a 20-mesh sieve, and the prescribed amount of magnesium stearate is added and mixed evenly; a single-layer osmotic pump tablet core is pressed using a circular shallow concave die with a diameter of 11.6 mm;

[0110] (2) Preparing a coating solution: weighing a prescribed amount of a semipermeable membrane coating material suspension, adding a prescribed amount of purified water to dilute it, and obtaining a coating solution;

[0111] (3) Coating: The tablet cores are coated with a coating solution, the coating weight gain is controlled to be 10%, and the coated products are aged at 40° C. for 12 h to obtain coated tablets; a drug release hole with a diameter of 0.4-1.2 mm is punched on the upper and lower sides of the coating film of the osmotic pump tablets using a laser.

[0112] Example 5

[0113] The present embodiment describes an osmotic pump controlled-release tablet of tranexamic acid, wherein the controlled-release tablet comprises a tablet core and an insoluble semipermeable coating membrane having drug-releasing holes; wherein:

[0114] The tablet core includes the following raw material ingredients (per tablet):

[0115]

[0116] The insoluble semipermeable coating film comprises the following raw material ingredients (based on tablet weight per 100g):

[0117] 80 ml of 25% solid content ethyl cellulose suspension;

[0118] 53.3ml of purified water.

[0119] The preparation process of the tranexamic acid monolayer osmotic pump controlled-release tablets described in this embodiment comprises the following steps:

[0120] (1) Wet granulation: The selected amount of tranexamic acid and excipients PVP-K30 and NaCl are crushed and dispersed through an 80-mesh sieve, then mixed evenly, a 5% PVP K30 aqueous solution is added to moisten the soft material, granulated through a 20-mesh sieve, dried at 40° C., the moisture content is controlled to be less than 3%, granulated through a 20-mesh sieve, and the prescribed amount of magnesium stearate is added and mixed evenly; a single-layer osmotic pump tablet core is pressed using a circular shallow concave die with a diameter of 11.6 mm;

[0121] (2) Preparing a coating solution: weighing a prescribed amount of a semipermeable membrane coating material suspension, adding a prescribed amount of purified water to dilute it, and obtaining a coating solution;

[0122] (3) Coating: The tablet cores are coated with a coating solution, the coating weight gain is controlled to be 15%, and the coated products are aged at 40° C. for 12 h to obtain coated tablets; a drug release hole with a diameter of 0.4-1.2 mm is punched on the upper and lower sides of the coating film of the osmotic pump tablets using a laser.

[0123] Example 6

[0124] The present embodiment describes an osmotic pump controlled-release tablet of tranexamic acid, wherein the controlled-release tablet comprises a tablet core and an insoluble semipermeable coating membrane having drug-releasing holes; wherein:

[0125] The tablet core includes the following raw material ingredients (per tablet):

[0126]

[0127] The insoluble semipermeable coating film comprises the following raw material ingredients (based on tablet weight per 100g):

[0128] 40 ml of 25% solid content ethyl cellulose suspension;

[0129] 26.7ml of purified water.

[0130] The preparation process of the tranexamic acid monolayer osmotic pump controlled-release tablets described in this embodiment comprises the following steps:

[0131] (1) Wet granulation: The selected amount of tranexamic acid and excipients PVP-K30 and NaCl are crushed and dispersed through an 80-mesh sieve, then mixed evenly, a 5% PVP K30 aqueous solution is added to moisten the soft material, granulated through a 20-mesh sieve, dried at 40° C., the moisture content is controlled to be less than 3%, granulated through a 20-mesh sieve, and the prescribed amount of magnesium stearate is added and mixed evenly; a single-layer osmotic pump tablet core is pressed using a circular shallow concave die with a diameter of 11.6 mm;

[0132] (2) Preparing a coating solution: weighing a prescribed amount of a semipermeable membrane coating material suspension, adding a prescribed amount of purified water to dilute it, and obtaining a coating solution;

[0133] (3) Coating: The tablet cores are coated with a coating solution, the coating weight gain is controlled to be 15%, and the coated products are aged at 40° C. for 12 h to obtain coated tablets; a drug release hole with a diameter of 0.4-1.2 mm is punched on the upper and lower sides of the coating film of the osmotic pump tablets using a laser.

[0134] Comparative Example 1

[0135] The comparative example describes an osmotic pump controlled-release tablet of tranexamic acid, which comprises a tablet core and an insoluble semipermeable coating membrane containing drug-releasing holes; wherein:

[0136] The tablet core includes the following raw material ingredients (per tablet):

[0137]

[0138] The insoluble semipermeable coating film comprises the following raw material ingredients (based on tablet weight per 100g):

[0139] 60 ml of 25% solid content ethyl cellulose suspension;

[0140] 40ml of purified water.

[0141] The preparation process of the tranexamic acid monolayer osmotic pump controlled-release tablets described in this embodiment comprises the following steps:

[0142] (1) Wet granulation: The selected amount of tranexamic acid and excipients PVP-K30 and NaCl are crushed and dispersed through an 80-mesh sieve, then mixed evenly, 5% PVP K30 ethanol solution is added to wet the soft material, granulated through a 20-mesh sieve, dried at 40° C., the moisture content is controlled to be less than 3%, granulated through a 20-mesh sieve, and the prescribed amount of magnesium stearate is added and mixed evenly; a single-layer osmotic pump tablet core is pressed using a circular shallow concave die with a diameter of 11.6 mm;

[0143] (2) Preparing a coating solution: weighing a prescribed amount of a semipermeable membrane coating material suspension, adding a prescribed amount of purified water to dilute it, and obtaining a coating solution;

[0144] (3) Coating: The tablet cores are coated with a coating solution, the coating weight gain is controlled to be 15%, and the coated products are aged at 40° C. for 12 h to obtain coated tablets; a drug release hole with a diameter of 0.4-1.2 mm is punched on the upper and lower sides of the coating film of the osmotic pump tablets using a laser.

[0145] Experimental example

[0146] 1. Release test

[0147] In this experimental example, the release of the tranexamic acid monolayer osmotic pump controlled-release tablets prepared in the above-mentioned Examples 1-6 and Comparative Example 1 was tested respectively. The specific determination method was according to the second method of the dissolution and release determination method of Part 0931 of the 2020 edition of the Pharmacopoeia of the People's Republic of China: 900 mL of pH 6.8 phosphate buffer solution was used as the release medium, the speed was 50 rpm, the temperature was (37 ± 0.5) ° C, and 10 mL was sampled at 0 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 14 h, 6 h, and 24 h, respectively. At the same time, an equal amount of fresh medium at the same temperature was supplemented, and the sample was filtered through a 0.45 μm microporous membrane. The peak area of ​​the filtrate was determined by high performance liquid chromatography, and the detection wavelength was 220 nm; another appropriate amount of reference substance was accurately weighed and determined by the same method. The cumulative release percentage was calculated by the external standard method, which should meet the requirements.

[0148] The in vitro release test results of the tranexamic acid monolayer osmotic pump controlled release tablets prepared in the above Examples 1-6 and Comparative Example 1 are shown in the attached Figure 1-7 shown.

[0149] It can be seen that in Examples 1-3, the in vitro drug release rate of the osmotic pump controlled release tablets is basically constant within 0-8h, showing an approximate zero-order release characteristic, about 80% is released at a constant rate within 8h, and slowly released after 8h, and the cumulative release is complete within 24h. The in vitro drug release of the osmotic pump controlled release tablets in Example 4 shows that the drug release rate is basically constant within the first 12h, showing an approximate zero-order release characteristic, about 80% is released at a constant rate within 12h, and slowly released after 12h, and the cumulative release is complete within 24h. The in vitro drug release of the osmotic pump controlled release tablets in Example 5 shows that the preparation has an in vitro cumulative release of less than 20% in the first 4h, and the drug release rate is basically constant within 4-12h, showing an approximate zero-order release characteristic, about 85% is released at a constant rate within 12h, and slowly released after 12h, and the cumulative release is complete within 24h. The in vitro drug release of the osmotic pump controlled release tablets in Example 6 and Comparative Example 1 shows that the drug release rate of the preparation is basically constant within 24h, showing an approximate zero-order release characteristic, and the cumulative release is complete within 24h.

[0150] The data of Example 4 and Comparative Example 1 were fitted and compared. The results are shown in Fig.11 As shown in the figure, when the dosage of release regulator NaCL remains unchanged and the type of penetration enhancer is changed, it can be seen that the difference in in vitro release of osmotic pump controlled release tablets when the penetration enhancers are equal dosages of PVP-K30 and PEO-WSR-N80. It can be seen that the osmotic pump controlled release tablets using PVP-K30 as a release regulator have a faster early release rate, and the drug release rate is basically constant in the first 12 hours, showing an approximate zero-order release characteristic, and a constant release of about 80% within 12 hours, and a slow release after 12 hours, and a cumulative complete release within 24 hours. The osmotic pump controlled release tablets using PEO-WSR-N80 as a penetration enhancer have a basically constant drug release rate within 24 hours, showing an approximate zero-order release characteristic, and a cumulative complete release within 24 hours.

[0151] The data of Examples 1-4 were fitted and compared, and the results are shown in Fig.12 That is, when the permeation enhancer remains unchanged, the difference in the in vitro release of the osmotic pump controlled-release tablets is found when the dosage of the permeation enhancer NaCl is changed. It can be seen that the release of the osmotic pump controlled-release tablets is accelerated with the increase of the dosage of NaCl, indicating that the dosage of NaCl affects the drug release rate of the osmotic pump controlled-release tablets.

[0152] The data of Examples 4-6 were fitted and compared, and the results are shown in Fig.13 That is, when the release regulator remains unchanged, the difference in the in vitro release of the osmotic pump controlled-release tablets is found when the dosage of the release regulator PVP-K30 is changed. It can be seen that the release of the osmotic pump controlled-release tablets first accelerates and then slows down with the increase in the dosage of PVP-K30, indicating that the dosage of PVP-K30 affects the drug release rate of the osmotic pump controlled-release tablets.

[0153] 2. Pharmacokinetics experiment in beagle dogs

[0154] In this experimental example, the tranexamic acid monolayer osmotic pump controlled-release tablets prepared in Example 1 were subjected to a beagle dog pharmacokinetic experiment.

[0155] Six Beagle dogs, half male and half female, were randomly divided into two groups according to gender and weight, with 3 dogs in each group. The clinical administration route of tranexamic acid monolayer osmotic pump controlled release tablets is oral administration, and the dosage for beagle dogs is 1 tablet / dog. The test dogs fasted overnight but could not be deprived of water (12h). One group took the reference preparation (common tablet 500mg) orally, and the other group took the test preparation (tablet of Example 1, 500mg) orally.

[0156] After one week of cleaning, the drugs were cross-administered and taken between 9:00 and 9:30 in the morning. The whole osmotic pump tablet was delivered into the epiglottis of the beagle dog's mouth. The dog was not allowed to drink water within 2 hours after taking the drug, and food was allowed to be taken 4 hours after taking the drug.

[0157] 2 mL of blood was collected from the upper limb vein of the test dogs before (0 hour) and 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours after each cycle of drug administration. The blood samples were placed in heparinized centrifuge tubes and centrifuged at 8000 r / min for 5 minutes. The upper plasma was aspirated and stored at -20°C for blood drug concentration determination.

[0158] The average blood drug concentration-time curves of the beagle dogs after oral administration of the reference preparation (ordinary tablets) are shown in the attached Figure 8 The average blood drug concentration-time curves of the beagle dogs after oral administration of the test preparations (osmotic pump controlled release tablets) are shown in the attached Fig. 9 As shown, the attached Figure 8 and 9 The curves shown in the figure were fitted on the same coordinate axis to obtain the average blood drug concentration-time curves of the beagle dogs after oral administration of the reference preparation (ordinary tablets) and the test preparation (osmotic pump controlled release tablets), as shown in the attached figure. Fig.10 shown.

[0159] It can be seen that compared with ordinary tablets, the relative bioavailability of tranexamic acid osmotic pump controlled-release tablets in animals is between 80% and 120%. The osmotic pump controlled-release tablets maintain a stable and effective blood drug concentration for a longer time, and the blood drug concentration fluctuation is significantly smaller, which fully reflects the excellent characteristics of sustained-release preparations. In addition, the osmotic pump controlled-release tablets release very little in the first two hours in the body, reducing gastrointestinal adverse reactions.

[0160] 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 therefrom are still within the scope of protection of the invention.

Claims

1. An osmotic pump controlled-release tablet of tranexamic acid, characterized in that, The controlled release tablet comprises a tablet core and an insoluble semipermeable coating film having drug release holes; wherein, The tablet core comprises the following raw material components in terms of total weight: 60-90 wt % of tranexamic acid, 2-30 wt % of a penetration enhancer, 2-30 wt % of a release regulator, 0.1-3 wt % of a lubricant, and 0.1-4 wt % of a wetting agent; The insoluble semipermeable coating film comprises the following raw material components in terms of weight: 90-100 wt % of semipermeable film-forming material, 0-10 wt % of pore-forming agent, and 0-10 wt % of plasticizer.

2. The osmotic pump controlled release tablet of tranexamic acid according to claim 1, characterized in that The tablet core comprises the following raw material and auxiliary material components in terms of total weight: 70-85wt% of tranexamic acid, 7-22wt% of penetration enhancer, 3-15wt% of release regulator, 1-2wt% of lubricant, and 1-2wt% of wetting agent.

3. The osmotic pump controlled release tablet of tranexamic acid according to claim 2, characterized in that, The tablet core comprises the following raw material and auxiliary material components in total weight: 71.94-84.03wt% of tranexamic acid, 7.46-21.58wt% of penetration enhancer, 3.60-14.93wt% of release regulator, 1.44-1.68wt% of lubricant, and 1.44-1.68wt% of wetting agent.

4. The osmotic pump controlled-release tablet of tranexamic acid according to any one of claims 1 to 3, characterized in that The insoluble semipermeable coating film comprises the following raw material components in terms of weight: 95-100 wt % of semipermeable film-forming material, 0-5 wt % of pore-forming agent, and 0-5 wt % of plasticizer.

5. The osmotic pump controlled-release tablet of tranexamic acid according to claim 4, characterized in that, The insoluble semipermeable coating membrane is prepared from a semipermeable membrane-forming material.

6. The osmotic pump controlled-release tablet of tranexamic acid according to any one of claims 1 to 5, characterized in that In the tablet core, the release regulator includes one or a mixture of several of hydroxypropyl methylcellulose, hydroxyethyl cellulose, polyoxyethylene, hydroxypropyl cellulose, polyvinyl pyrrolidone, sodium alginate or guar gum.

7. The osmotic pump controlled-release tablet of tranexamic acid according to claim 6, characterized in that In the tablet core, the penetration enhancer includes one or a mixture of sodium chloride, potassium chloride, glucose, sucrose, lactose, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, d-mannitol, urea, magnesium succinate, sorbitol or tartaric acid.

8. The osmotic pump controlled-release tablet of tranexamic acid according to claim 6 or 7, characterized in that, In the tablet core, the lubricant includes one or a mixture of magnesium stearate, talc, colloidal silicon dioxide, sodium stearyl fumarate or magnesium lauryl sulfate.

9. The osmotic pump controlled-release tablet of tranexamic acid according to any one of claims 6 to 8, characterized in that: In the tablet core, the wetting agent includes polyvinyl pyrrolidone and / or ethanol.

10. The osmotic pump controlled-release tablet of tranexamic acid according to any one of claims 1 to 9, characterized in that: In the insoluble semipermeable coating film, the semipermeable film-forming material includes one or a mixture of cellulose acetate, ethyl cellulose or acrylic resin.

11. The osmotic pump controlled-release tablet of tranexamic acid according to claim 10, characterized in that: In the insoluble semipermeable coating film, the pore-forming agent includes one or a mixture of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene glycol, propylene glycol, a water-soluble inorganic salt or polyvinyl pyrrolidone.

12. The osmotic pump controlled-release tablet of tranexamic acid according to claim 10 or 11, characterized in that: In the insoluble semipermeable coating film, the plasticizer includes one or a mixture of glycerol, polyethylene glycol, triacetin, castor oil, acetylated monoglyceride or phthalate.

13. The osmotic pump controlled-release tablet of tranexamic acid according to any one of claims 1 to 12, characterized in that: The tablet core comprises the following raw material and auxiliary material components in total amount: 71.94-84.03wt% of tranexamic acid, 7.46-21.58wt% of sodium chloride, 3.60-14.93wt% of polyvinyl pyrrolidone, 1.44-1.68wt% of magnesium stearate, and 1.44-1.68wt% of wetting agent; wherein the wetting agent is an aqueous solution prepared with a selected amount of polyvinyl pyrrolidone; The insoluble semipermeable coating film comprises the following raw material components in terms of weight: 100 wt % of ethyl cellulose.

14. The osmotic pump controlled-release tablet of tranexamic acid according to claim 13, characterized in that: Each osmotic pump controlled-release tablet of tranexamic acid contains: The tablet core comprises: 100 mg of tranexamic acid, 50 mg of PVP K30, 50 mg of sodium chloride, 10 mg of magnesium stearate, and 0.2 ml of 5% PVP K30 aqueous solution; The insoluble semipermeable coating film comprises ethyl cellulose, and the weight gain of the insoluble semipermeable coating film is 10-20 wt %.

15. The osmotic pump controlled-release tablet of tranexamic acid according to claims 1-14, characterized in that: The mass ratio of the insoluble semipermeable coating film to the tablet core is 5-20:

100.

16. The osmotic pump controlled-release tablet of tranexamic acid according to claim 15, characterized in that: The mass ratio of the insoluble semipermeable coating film to the tablet core is 10-20:

100.

17. The osmotic pump controlled-release tablet of tranexamic acid according to any one of claims 1 to 16, characterized in that: The drug-releasing holes are distributed on both sides of the surface of the insoluble semipermeable coating membrane.

18. The osmotic pump controlled-release tablet of tranexamic acid according to claim 17, characterized in that: The diameter of the drug release hole is 0.4 mm-1.2 mm.

19. The osmotic pump controlled-release tablet of tranexamic acid according to any one of claims 1 to 18, characterized in that: The osmotic pump controlled-release tablet is a tranexamic acid single-layer osmotic pump tablet preparation; In the controlled-release tablet, the cumulative release percentage of tranexamic acid in 12 hours is 50-90%, and the cumulative release percentage of the drug in 24 hours is 80-100%. Zero-order release can be maintained within 12 hours without release lag, ensuring that the drug can take effect quickly while maintaining a stable blood drug concentration in the body, reducing toxic side effects.

20. A method for preparing an osmotic pump controlled-release tablet of tranexamic acid according to any one of claims 1 to 19, characterized in that: The steps include: (1) taking selected amounts of the tranexamic acid, the penetration enhancer, and the release regulator, mixing them, adding the wetting agent to form a soft material, sieving and granulating, and drying, continuing to add the lubricant to mix, and pressing to obtain a single-layer osmotic pump tablet core; (2) taking a selected amount of the semipermeable membrane-forming material, pore-forming agent and plasticizer, adding water and mixing to form a coating solution; (3) coating the core tablet with the coating liquid to obtain the desired coated tablet, and forming the desired drug release holes on both sides of the coated tablet.

21. The method for preparing the osmotic pump controlled-release tablet of tranexamic acid according to claim 20, characterized in that: In the step (2), the concentration of the coating solution is controlled to be 5-30 wt %.

22. The method for preparing the osmotic pump controlled-release tablet of tranexamic acid according to claim 20 or 21, characterized in that: The step (3) further comprises the step of subjecting the coated tablet to an aging treatment; The temperature of the aging treatment step is 30-50° C., and the aging treatment time is 10-15 hours.

23. Use of the osmotic pump controlled-release tablet of tranexamic acid according to any one of claims 1 to 19 for preparing a medicament for treating menorrhagia symptoms.

24. The use according to claim 23, characterized in that The menorrhagia includes idiopathic menorrhagia.

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