A pegaptanib composition and a method for preparing the same

Abstract

This invention discloses a pulcanapeptide composition and its preparation method. Specifically, this invention provides a pulcanapeptide pharmaceutical composition comprising the following components by mass percentage: 1.5%-9% pulcanapeptide, 90%-98.4% filler, and 0.1%-1% lubricant; the particle size D90 of the pulcanapeptide is ≤100μm, and the pulcanapeptide pharmaceutical composition is prepared by direct powder compression or dry granulation followed by tableting. The pulcanapeptide composition provided by this invention has the advantages of high dissolution efficiency and high stability. The direct powder compression or dry granulation followed by tableting process of this application can reduce production costs and is more suitable for industrial production.

Description

[0001] This application claims priority to Chinese patent application 2025119220497, filed on December 18, 2025, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This invention relates to the field of pharmaceutical formulations, and more specifically, to a pharmaceutical composition of purcanatide and excipients, and a method for preparing the same. The pharmaceutical composition of this invention is used to treat functional constipation (FC) and related conditions such as constipation-predominant irritable bowel syndrome (IBS-C) in adults. Background Technology

[0003] Constipation-predominant irritable bowel syndrome (IBS-C) and functional constipation (FC) are two common functional gastrointestinal disorders. Their onset is related to abnormal colonic and anorectal motility, as well as psychological factors. The global prevalence is 12%–17% and 11.2%, respectively. Both can manifest as difficulty in defecation, hard, dry, and small stools, reduced bowel movement frequency, and symptoms such as abdominal pain, bloating, and discomfort. Functional constipation (FC) is primarily characterized by constipation, while constipation-predominant irritable bowel syndrome (IBS-C) is primarily characterized by abdominal pain, bloating, and discomfort. Both can negatively impact the work and quality of life of modern individuals to varying degrees.

[0004] Pucanatide is a synthetic human gastrin-releasing peptide analog that increases the secretion of water and electrolytes in the colon by activating gastrin-releasing peptide receptors, thereby softening stool and promoting defecation, helping to improve constipation symptoms. Therefore, pulcanatide is used to treat functional constipation (FC) and constipation-predominant irritable bowel syndrome (IBS-C) in adults. For patients with chronic idiopathic constipation or IBS-C, pulcanatide can help improve bowel frequency and stool consistency, reduce bloating and abdominal pain, and has fewer adverse reactions than linaclotide. In clinical trials, the dropout rate due to severe diarrhea was significantly lower with linaclotide. In one clinical trial for treating FC, the diarrhea rate with pulcanatide was <6%, while with linaclotide it was 16%. The current dosage form of pulcanatide is pulcanatide tablets, and its manufacturing process has strict requirements on the water content of excipients. Therefore, a new manufacturing process needs to be developed to reduce production costs and make it more suitable for industrial production. Summary of the Invention

[0005] The purpose of this invention is to provide a purcanapeptide composition for treating constipation, particularly suitable for treating constipation-predominant irritable bowel syndrome (IBS-C) and functional constipation (FC), filling a gap in the domestic market. The purcanapeptide composition provided by this invention has the advantages of high dissolution efficiency and high stability. The powder direct compression or dry granulation process of this application can reduce production costs and is more suitable for industrial production.

[0006] This invention provides a purcanatide pharmaceutical composition comprising the following components by weight percentage: 1.5%-9% purcanatide, 90%-98.4% filler, and 0.1%-1% lubricant; wherein the purcanatide has a particle size D90≤100μm, and the purcanatide pharmaceutical composition is prepared by direct powder compression or dry granulation followed by tableting.

[0007] In this invention, the percentage of each component in the pulcanapeptide pharmaceutical composition is its percentage of the total mass of the pulcanapeptide pharmaceutical composition.

[0008] In one embodiment, the mass percentage of the purcanapeptide is 3%-9%, preferably 3%-6%.

[0009] In one embodiment, the filler is selected from one or more of microcrystalline cellulose, mannitol, lactose, and starch, such as microcrystalline cellulose.

[0010] In one embodiment, the filler has a mass percentage of 90.5%-96.8%, preferably 93%-96%, for example 93.8%.

[0011] In one embodiment, the lubricant is selected from one or both of magnesium stearate and sodium stearate fumarate, for example, magnesium stearate.

[0012] In one embodiment, the mass percentage of the lubricant is 0.2%-0.5%.

[0013] In one embodiment, the particle size D90 of the purcanatide is 3μm-100μm, for example 5μm-95μm, for example 10μm-80μm, for example 30μm-72μm, and for example 50μm-66μm.

[0014] In this invention, the water content of the filler refers to the percentage of the mass of water in the filler relative to the total mass of the filler.

[0015] In one embodiment, the filler has a water content of ≤6.5%, ≤5.9%, ≤4.5%, or ≤3.7%.

[0016] In one embodiment, the filler is obtained by purchasing commercially available materials or by drying commercially available materials.

[0017] In one embodiment, each unit of the purcanatide pharmaceutical composition contains 2 mg to 9 mg of purcanatide, for example, 3 mg to 6 mg.

[0018] In one embodiment, the purcanatide pharmaceutical composition is a tablet.

[0019] In one embodiment, the hardness of the tablet is 30~70N.

[0020] In one embodiment, the pulcanatide pharmaceutical composition comprises 1.5% - 9% pulcanatide, 90% - 98.4% microcrystalline cellulose, and 0.1% - 1% magnesium stearate.

[0021] In one embodiment, the mass percentages of pulcanapeptide, microcrystalline cellulose, and magnesium stearate in the pulcanapeptide pharmaceutical composition are selected from any of the following: .

[0022] In one embodiment, the direct powder compression process includes the following steps: directly compressing the total mixed powder of the purcanapeptide, the filler, and the lubricant into tablets to obtain the purcanapeptide pharmaceutical composition.

[0023] In one embodiment, the dry granulation followed by tableting process includes the following steps: dry granulation and tableting of the total mixture of the purcanatide, the filler, and the lubricant to obtain the purcanatide pharmaceutical composition.

[0024] In one embodiment, the preparation method of the total mixed powder includes the following steps: Step (I): Divide the prescribed amount of filler into N portions, where N≥2 and N is an integer; Step (II): Mix one portion of the filler from step (I) with the prescribed amount of purcanapeptide; Step (III): The mixture obtained after the mixing in step (II) is mixed with one part of the filler in step (I) each time, until all N-1 parts of the filler are mixed to obtain mixture B; Step (IV): Mix the mixture B with the prescribed amount of lubricant to obtain a total powder mixture.

[0025] In one possible solution, N can be 2, 3, 4, 5, or 6.

[0026] In one embodiment, each of the N portions of filler has the same mass.

[0027] In one embodiment, after step (I) and before step (II), a portion of the filler described in step (II) is first placed in a mixer for mixing, preferably for 3 minutes.

[0028] In one scheme, each of the mixing steps (II), (III) and (IV) is a uniform mixing.

[0029] In one embodiment, after the powder direct pressing process and the dry granulation followed by tableting process are completed, a packaging step is independently included, for example, packaging the obtained tablet purcanatae composition in plastic bottles (containing polyester fibers and desiccant) or aluminum blister packs (containing desiccant coating).

[0030] In one embodiment, the preparation method of the purcanatide pharmaceutical composition includes the following steps (a), (b), and (c): Step (a): Weigh the prescribed amount of filler and divide it into N parts. First, mix 1 part of microcrystalline cellulose with the prescribed amount of purcanapeptide. Add the remaining N-1 parts of filler one at a time and mix evenly until all of them are added. Finally, add the prescribed amount of lubricant and mix to obtain the total powder. Step (b): The total mixed powder obtained in step (a) is directly compressed into tablets or dry granulated and then compressed into tablets to obtain uncoated tablets, wherein the hardness of the tablets is controlled at 30~70N; Step (c): Package the raw film obtained in step (b) into plastic bottles.

[0031] This invention provides a method for preparing the purcanatide pharmaceutical composition, wherein the preparation method employs a direct powder compression process or a dry granulation process, and includes the following steps: The powder direct compression process includes the following steps: directly compressing the total mixed powder of the purcanapeptide, the filler and the lubricant into tablets to obtain the purcanapeptide pharmaceutical composition; The dry granulation and tableting process includes the following steps: dry granulation and tableting of the total mixed powder of the purcanapeptide, the filler and the lubricant to obtain the purcanapeptide pharmaceutical composition; The operation and conditions of the powder direct compression process and the dry granulation followed by tableting process can independently be as described in any of the preceding schemes.

[0032] In this invention, particle size D90 is a commonly used particle size distribution parameter used to describe the particle size distribution characteristics of a particle population. Specifically, D90 indicates that 90% of the particles in the particle size distribution have a diameter less than or equal to this value.

[0033] In this invention, the dry granulation followed by tableting process adopts conventional conditions in the art.

[0034] Based on common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0035] The reagents and raw materials used in this invention are all commercially available.

[0036] Compared with the prior art, the present invention has the following beneficial effects: (1) The purcanatide composition of the present invention fills the gap in the domestic market and increases the medication options for domestic patients; after taking it, it can disintegrate rapidly in the body, ensuring that the drug dissolves quickly and acts on the target on the gastrointestinal epithelial cells, so as to exert its therapeutic effect rapidly.

[0037] (2) By examining the particle size of purcanapeptide (D90≤100μm) and the mixing process of each component (RSD of purcanapeptide content in total mixed powder ≤0.7% (RSD represents relative standard deviation)), this invention developed a powder direct compression and dry granulation tableting process for purcanapeptide drug composition. The production process is simple, does not require drying, avoids contact with moisture and heat, and saves energy and time. It has a more relaxed requirement for the moisture content of fillers and is suitable for a wider range of fillers.

[0038] (3) The purcanapeptide composition of the present invention is a tablet, which is convenient to use, easy to store and transport, simple to prepare, easy to industrialize and produce, and has low production cost. During preparation and long-term storage, the product can maintain rapid dissolution (≥85% in 15min) and good stability. Detailed Implementation

[0039] The beneficial effects of the present invention will be further described through the following embodiments. These embodiments are for illustrative purposes only and do not limit the scope of the present invention. Obvious changes and modifications made by those skilled in the art based on the present invention are also included within the scope of the present invention. All technical contents not described in detail in this invention are publicly known technologies.

[0040] In the following performance test examples, the chemical structure of impurity 1 is as follows (SEQ ID 01): H-Asn1-iso-Asp2-Glu3-Cys4-Glu5-Leu6-Cys7-Val8-Asn9-Val10-Ala11-Cys12-Thr13-Gly14-Cys15-Leu16-OH (Disulfide bonds exist between Cys4 and Cys12, and between Cys7 and Cys15).

[0041] The structure of impurity 2 is as follows (SEQ ID 02): H-Asn1-Glu2-Cys3-Glu4-Leu5-Cys6-Val7-Asn8-Val9-Ala10-Cys11-Thr12-Gly13-Cys14-Leu15-OH (disulfide bonds exist between Cys3 and Cys11, and between Cys6 and Cys14).

[0042] Example 1

[0043] A type of purcanapeptide tablet is composed of the raw materials and excipients shown in Table 1 below: Table 1

[0044] Preparation method (5000 tablets): (1) Weigh the prescribed amount of microcrystalline cellulose (the commercially available sample with a moisture content of 7.5% was further dried and the moisture content was adjusted to 4.5% (similar drying methods were used to obtain the corresponding moisture content in the following examples)) and divide it into 5 portions. First, add 1 portion of microcrystalline cellulose to the mixer and mix for 3 minutes. Then, add the prescribed amount of purcanapeptide (D90=50μm) and mix evenly. Add the remaining 4 portions of microcrystalline cellulose one portion at a time and mix evenly until all the cellulose is added. Finally, add the prescribed amount of magnesium stearate and mix evenly. After mixing, use a sampler to take 10 samples from different locations of the total mixed powder to test the mixing uniformity (the results are shown in Table 11). (2) The total mixed powder obtained in step (1) is directly compressed into tablets to obtain raw tablets, wherein the hardness of the tablets is controlled at 30~70N.

[0045] (3) Pack the raw film obtained in step (2) into plastic bottles (the bottles contain polyester fiber and desiccant).

[0046] Example 2

[0047] A type of purcanapeptide tablet is composed of the raw materials and excipients shown in Table 2 below: Table 2

[0048] Preparation method (5000 tablets): (1) Weigh out the prescribed amount of microcrystalline cellulose (moisture content is 3.7%) and divide it into 5 portions. First, add 1 portion of microcrystalline cellulose to the mixer and mix for 3 minutes. Then add the prescribed amount of purcanapeptide (D90=10μm) and mix evenly. Add the remaining 4 portions of microcrystalline cellulose one portion at a time and mix evenly until all of them are added. Finally, add the prescribed amount of magnesium stearate and mix evenly. (2) The total mixed powder obtained in step (1) is directly compressed into tablets to obtain raw tablets, wherein the hardness of the tablets is controlled at 30~70N.

[0049] (3) Pack the raw film obtained in step (2) into plastic bottles (the bottles contain polyester fiber and desiccant).

[0050] Example 3

[0051] A type of purcanapeptide tablet is composed of the raw materials and excipients shown in Table 3 below: Table 3

[0052] Preparation method (5000 tablets): (1) Weigh out the prescribed amount of microcrystalline cellulose (moisture content is 1.4%) and divide it into 5 portions. First, add 1 portion of microcrystalline cellulose to the mixer and mix for 3 minutes. Then add the prescribed amount of purcanapeptide (D90=30μm) and mix evenly. Add the remaining 4 portions of microcrystalline cellulose one portion at a time and mix evenly until all of them are added. Finally, add the prescribed amount of magnesium stearate and mix evenly. (2) The total mixed powder obtained in step (1) is directly compressed into tablets to obtain raw tablets, wherein the hardness of the tablets is controlled at 30~70N.

[0053] (3) Pack the raw film obtained in step (2) into plastic bottles (the bottles contain polyester fiber and desiccant).

[0054] Example 4

[0055] A type of purcanapeptide tablet is composed of the raw materials and excipients shown in Table 4 below: Table 4

[0056] Preparation method (5000 tablets): (1) Weigh out the prescribed amount of microcrystalline cellulose (moisture content of 2.4%) and divide it into 5 portions. First, add 1 portion of microcrystalline cellulose to the mixer and mix for 3 minutes. Then add the prescribed amount of purcanapeptide (D90=72μm) and mix evenly. Add the remaining 4 portions of microcrystalline cellulose one portion at a time and mix evenly until all the cellulose is added. Finally, add the prescribed amount of magnesium stearate and mix evenly. (2) The total mixed powder obtained in step (1) is granulated by dry method and then compressed into tablets to obtain plain tablets, wherein the hardness of the tablets is controlled at 30~70N.

[0057] (3) Pack the raw film obtained in step (2) into plastic bottles (the bottles contain polyester fiber and desiccant).

[0058] Example 5

[0059] A type of purcanapeptide tablet is composed of the raw materials and excipients shown in Table 5 below: Table 5

[0060] Preparation method (5000 tablets): (1) Weigh out the prescribed amount of microcrystalline cellulose (moisture content is 5.9%) and divide it into 5 portions. First, add 1 portion of microcrystalline cellulose to the mixer and mix for 3 minutes. Then add the prescribed amount of purcanapeptide (D90=95μm) and mix evenly. Add the remaining 4 portions of microcrystalline cellulose one portion at a time and mix evenly until all of them are added. Finally, add the prescribed amount of magnesium stearate and mix evenly. (2) The total mixed powder obtained in step (1) is directly compressed into tablets to obtain raw tablets, wherein the hardness of the tablets is controlled at 30~70N.

[0061] (3) Pack the raw film obtained in step (2) into plastic bottles (the bottles contain polyester fiber and desiccant).

[0062] Example 6

[0063] A type of purcanapeptide tablet is composed of the raw materials and excipients shown in Table 6 below: Table 6

[0064] Preparation method (5000 tablets): (1) Weigh out the prescription amount of microcrystalline cellulose (moisture content of 6.5%) and divide it into 5 portions. First, add 1 portion of microcrystalline cellulose to the mixer and mix for 3 minutes. Then add the prescription amount of purcanapeptide (D90=66μm) and mix evenly. Add the remaining 4 portions of microcrystalline cellulose one portion at a time and mix evenly until all of them are added. Finally, add the prescription amount of magnesium stearate and mix evenly. (2) The total mixed powder obtained in step (1) is directly compressed into tablets to obtain raw tablets, wherein the hardness of the tablets is controlled at 30~70N.

[0065] (3) Pack the raw film obtained in step (2) into plastic bottles (the bottles contain polyester fiber and desiccant).

[0066] Comparative Example 1

[0067] A type of purcanapeptide tablet is composed of the raw materials and excipients shown in Table 7 below: Table 7

[0068] Preparation method (5000 tablets): (1) Weigh out the prescribed amount of microcrystalline cellulose (moisture content of 4.5%) and divide it into two portions. First, add one portion of microcrystalline cellulose to a wet granulator and mix for 3 minutes. Then add the prescribed amount of purcanapeptide (D90=50μm) and the remaining portion of microcrystalline cellulose to the wet granulator and mix evenly. Add an appropriate amount of purified water to granulate (the soft material can be clumped when squeezed and dispersed when lightly pressed). Use a fluidized bed and set the air inlet temperature to 45℃ to dry the wet granules. (2) Based on the dry particle yield obtained in step (1), calculate the amount of magnesium stearate to be added, and add the calculated magnesium stearate and mix evenly. (3) The total mixed powder obtained in step (2) is directly compressed into tablets to obtain raw tablets, wherein the hardness of the tablets is controlled at 30~70N.

[0069] (4) Pack the raw film obtained in step (3) into plastic bottles (the bottles contain polyester fiber and desiccant).

[0070] Comparative Example 2

[0071] A type of purcanapeptide tablet is composed of the raw materials and excipients shown in Table 8 below: Table 8

[0072] Preparation method (5000 tablets): (1) Weigh out the prescribed amount of microcrystalline cellulose (moisture content of 4.5%) and divide it into 5 portions. First, add 1 portion of microcrystalline cellulose to the mixer and mix for 3 minutes. Then add the prescribed amount of purcanapeptide (D90=110μm) and mix evenly. Add the remaining 4 portions of microcrystalline cellulose one portion at a time and mix evenly until all the cellulose is added. Finally, add the prescribed amount of magnesium stearate and mix evenly. After mixing, use a sampler to take 10 samples from different locations of the material to test the mixing uniformity (the results are shown in Table 11). (2) The total mixed powder obtained in step (1) is directly compressed into tablets to obtain raw tablets, wherein the hardness of the tablets is controlled at 30~70N.

[0073] (3) Pack the raw film obtained in step (2) into plastic bottles (the bottles contain polyester fiber and desiccant).

[0074] Comparative Example 3

[0075] A type of purcanatae tablet is composed of the raw materials and excipients shown in Table 9 below: Table 9

[0076] Preparation method (5000 tablets): (1) Weigh out the prescribed amount of microcrystalline cellulose (moisture content of 4.5%) and divide it into 5 portions. First, add 1 portion of microcrystalline cellulose to the mixer and mix for 3 minutes. Then add the prescribed amount of purcanapeptide (D90=3μm) and mix evenly. Add the remaining 4 portions of microcrystalline cellulose one portion at a time and mix evenly until all portions are added. Finally, add the prescribed amount of magnesium stearate and mix evenly. After mixing, use a sampler to take 10 samples from different locations of the material to test the mixing uniformity (the results are shown in Table 12). (2) The total mixed powder obtained in step (1) is directly compressed into tablets to obtain raw tablets, wherein the hardness of the tablets is controlled at 30~70N.

[0077] (3) Pack the raw film obtained in step (2) into plastic bottles (the bottles contain polyester fiber and desiccant).

[0078] Experimental results: (1) Disintegration test: The disintegration time was tested according to the Disintegration Time Test Method in General Chapter 0921 of Part IV of the 2020 Chinese Pharmacopoeia. The disintegration time test results of the uncoated tablets in Examples 1-6 are shown in Table 10. Specific method: The basket was suspended from the support by the upper stainless steel shaft and immersed in a 1000ml beaker. The position of the basket was adjusted so that when it was lowered to the lowest point, the sieve was 25mm from the bottom of the beaker. The beaker contained water at a temperature of 37℃±2℃. The water level was adjusted so that when the basket was raised to the highest point, the sieve was 15mm below the water surface. The top of the basket should not be submerged in the solution. Complete disintegration refers to the complete disintegration or fragmentation of the oral solid dosage form under specified conditions. Except for insoluble coating materials or broken capsule shells, all should pass through the sieve. If a small amount cannot pass through the sieve or adheres to the lower surface of the baffle, but has softened or floated lightly without a noticeable hard core, it meets the requirements.

[0079] (2) The content was determined by high performance liquid chromatography (HPLC) according to the General Chapter 0512 of the 2020 edition of the Chinese Pharmacopoeia (Tables 10, 13 and 14). The content / % refers to the mass of purcanapeptide in the tablets determined by HPLC 0512 / the mass of purcanapeptide actually added to the tablets. 100%).

[0080] (3) Dissolution was tested according to the second method of Dissolution and Release Determination Method 0931, Part IV, Chinese Pharmacopoeia 2020 Edition. The dissolution test results of the tablets in Examples 1-6 are shown in Table 10.

[0081] Table 10

[0082] The results in Table 10 show that, compared to the powder direct compression process / dry granulation followed by tableting used in Examples 1-6, the tablet content and dissolution rate of Comparative Example 1 obtained by wet granulation according to the formulation of the examples were both lower and did not meet the requirements. No further stability studies were conducted on the sample of Comparative Example 1.

[0083] (4) Mixing uniformity test in Example 1 and Comparative Examples 2 and 3

[0084] The mixing uniformity of the total powder mixtures of the formulations described in Example 1 and Comparative Examples 2 and 3 was tested, and the results are detailed in Tables 11-12. The mixing uniformity was tested according to the high-performance liquid chromatography method in General Chapter 0512 of the Chinese Pharmacopoeia, referring to the "Technical Guidelines for the Study of Mixing Uniformity and Controlled Dosage Unit Uniformity of Oral Solid Dosage Forms of Chemical Drugs (Trial Implementation)," with a mixing uniformity RSD limit of ≤5.0%. At least 10 sampling points were selected throughout the batch, with one sample tested at each sampling point, and the relative standard deviation (RSD) of all samples was calculated (n≥10).

[0085] Table 11

[0086] Table 12

[0087] In Tables 11 and 12, the percentage of purcanapeptide content refers to the mass of purcanapeptide detected in the sample / the mass of the sample. 100%.

[0088] The results in Tables 11 and 12 show that the RSD of the total powder mixture prepared in Example 1 and Comparative Example 3 is 0.70% and 4.93%, respectively, which is less than 5.0%. However, in the formulation described in Comparative Example 2, the particle size of the purcanapeptide raw material is controlled at D90=110μm, and the RSD of the total powder mixture is 8.6%, which is greater than 5.0%. This indicates that when the particle size of the purcanapeptide raw material increases, the uniformity of the total powder mixture does not meet the pharmaceutical requirements. Therefore, the purcanapeptide raw material particle size controlled by the present invention, D90≤100μm, has good stability and dissolution effect.

[0089] (4) Stability test

[0090] The formulations described in this invention (Examples 1-6) were subjected to accelerated stability tests and long-term stability tests, respectively.

[0091] Test conditions and methods: After being placed under accelerated conditions (40℃±2℃ / 75%RH±5%RH) for 6 months, samples were taken at 1 month, 3 months and 6 months to test the content (limits are 90.0~110.0%, the same below), dissolution (limits are ≥80% dissolution at 30 minutes), and related substances (limits are ≤1.5% for impurity 1, ≤1.0% for impurity 2, and ≤5.0% for total impurities, the same below); after being placed under long-term conditions (25℃±2℃ / 60%RH±5%RH) for 36 months, samples were taken at 12 months, 24 months and 36 months to test the content, dissolution and related substances.

[0092] (A) The results of the accelerated stability test are shown in Table 13 below: Table 13

[0093] (B) The results of the long-term stability test are shown in Table 14 below: Table 14

[0094] The results in Tables 13 and 14 show that the formulations prepared by direct powder compression or dry granulation of the present invention (Examples 1-6, with microcrystalline cellulose moisture content controlled at ≤6.5%) showed good stability after accelerated (40℃±2℃ / 75%RH±5%RH) and long-term (25℃±2℃ / 60%RH±5%RH) stability tests. Preferably, when the microcrystalline cellulose moisture content is controlled at ≤5.9% (e.g., Examples 1-5), the resulting formulations have lower impurity content and better stability.

Claims

1. A purcanatide pharmaceutical composition, characterized in that, It comprises the following components by mass percentage: 1.5% - 9% purcanapeptide, 90% - 98.4% filler and 0.1% - 1% lubricant; the particle size D90 of the purcanapeptide is ≤100μm, and the purcanapeptide pharmaceutical composition is prepared by direct powder compression or dry granulation followed by tableting.

2. The purcanatide pharmaceutical composition according to claim 1, characterized in that, It meets one or more of the following conditions: (1) The mass percentage of the pulcanapeptide is 3%-9%; (2) The filler is selected from one or more of microcrystalline cellulose, mannitol, lactose and starch; (3) The mass percentage of the filler is 90.5%-96.8%; (4) The lubricant is selected from one or both of magnesium stearate and sodium stearate fumarate; (5) The mass percentage of the lubricant is 0.2%-0.5%; (6) The particle size D90 of the purcanapeptide is 3 μm - 100 μm; (7) The water content of the filler is ≤6.5%; (8) Each unit of the pharmaceutical composition contains 2-9 mg of purcanapeptide; (9) The pharmaceutical composition is a tablet; (10) The filler is obtained by purchasing commercially available materials or by drying commercially available materials.

3. The purcanatide pharmaceutical composition according to claim 2, characterized in that, It meets one or more of the following conditions: (1) The mass percentage of the pulcanapeptide is 3%-6%; (2) The filler is microcrystalline cellulose; (3) The mass percentage of the filler is 93%-96%; (4) The lubricant is magnesium stearate; (5) The mass percentage of the lubricant is 0.2%-0.5%; (6) The particle size D90 of the purcanapeptide is 30μm-72μm; (7) The water content of the filler is ≤5.9%; (8) Each unit of the pharmaceutical composition contains 3-6 mg of purcanapeptide; (9) The hardness of the tablet is 30~70N.

4. The purcanatide pharmaceutical composition according to claim 3, characterized in that, It meets one or more of the following conditions: (1) The filler has a mass percentage of 93.8%; (2) The particle size D90 of the purcanapeptide is 50 μm-66 μm; (3) The water content of the filler is ≤4.5%, for example ≤3.7%.

5. The purcanatide pharmaceutical composition according to claim 1, characterized in that, The pharmaceutical composition comprises the following components in weight percentages: 1.5% - 9% purcanatide, 90% - 98.4% microcrystalline cellulose, and 0.1% - 1% magnesium stearate.

6. The purcanatide pharmaceutical composition according to claim 5, characterized in that, In the pharmaceutical composition, the mass percentages of purcanapeptide, microcrystalline cellulose, and magnesium stearate are selected from any of the following: 。 7. The purcanatide pharmaceutical composition according to any one of claims 1-6, characterized in that, The powder direct compression process includes the following steps: directly compressing the total mixed powder of the purcanapeptide, the filler and the lubricant into tablets to obtain the purcanapeptide pharmaceutical composition; Alternatively, the dry granulation and tableting process may include the following steps: dry granulating and tableting the total mixture of the purcanatide, the filler, and the lubricant to obtain the purcanatide pharmaceutical composition.

8. The purcanatide pharmaceutical composition according to claim 7, characterized in that, The preparation method of the total mixed powder includes the following steps: Step (I): Divide the prescribed amount of filler into N portions, where N≥2 and N is an integer; Step (II): Mix one portion of the filler from step (I) with the prescribed amount of purcanapeptide; Step (III): The mixture obtained after the mixing in step (II) is mixed with one part of the filler in step (I) each time, until all N-1 parts of the filler are mixed to obtain mixture B; Step (IV): Mix the mixture B with the prescribed amount of lubricant to obtain a total powder mixture.

9. The purcanatide pharmaceutical composition according to claim 8, characterized in that, It meets one or more of the following conditions: (1) N is 2, 3, 4, 5 or 6; (2) Each of the N portions of filler has the same mass; (3) After step (I) and before step (II), one portion of the filler described in step (II) is first placed in a mixer and mixed, preferably for 3 minutes; (4) In steps (II), (III) and (IV), each of the mixing steps is a uniform mixing; (5) The preparation method of the purcanatide pharmaceutical composition includes the following steps (a), (b) and (c): Step (a): Weigh the prescribed amount of filler and divide it into N parts. First, mix 1 part of microcrystalline cellulose with the prescribed amount of purcanapeptide. Add the remaining N-1 parts of filler one at a time and mix evenly until all of them are added. Finally, add the prescribed amount of lubricant and mix to obtain the total powder. Step (b): The total mixed powder obtained in step (a) is directly compressed into tablets or dry granulated and then compressed into tablets to obtain uncoated tablets, wherein the hardness of the tablets is controlled at 30~70N; Step (c): Package the raw film obtained in step (b) into plastic bottles.

10. A method for preparing the purcanatide pharmaceutical composition according to any one of claims 1-7, characterized in that, The preparation method employs either direct powder compression or dry granulation followed by tableting. The powder direct compression process includes the following steps: directly compressing the total mixed powder of the purcanapeptide, the filler and the lubricant into tablets to obtain the purcanapeptide pharmaceutical composition; The dry granulation and tableting process includes the following steps: dry granulation and tableting of the total mixed powder of the purcanapeptide, the filler and the lubricant to obtain the purcanapeptide pharmaceutical composition; The operation and conditions of the powder direct compression and dry granulation followed by tableting processes can also be independently described as in claim 8 or 9.

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