Bruxpiprazole dropping pill and preparation method thereof

Abstract

The invention provides a brexpiprazole dropping pill and a preparation method thereof, and relates to the technical field of medicine, the brexpiprazole dropping pill comprises brexpiprazole and a dropping pill matrix, the weight part ratio of the brexpiprazole to the dropping pill matrix is 10: 138-356; the dripping pill matrix comprises polyethylene glycol, 70% acetic acid and poloxamer, and the 70% acetic acid is used as a solubilizer to promote dissolution of brexpiprazole and poloxamer under a stirring condition; the poloxamer is used as a penetration enhancer, so that the transdermal effect is remarkably improved; the polyethylene glycol, the 70% acetic acid and the poloxamer are used as dropping pill matrixes to be matched with the brexpiprazole to obtain the spherical dropping pill with sufficient hardness and stability and good dissolution rate. The technical problem that in the prior art, a brexpiprazole tablet or orally disintegrating tablet cannot be rapidly dissolved, so that the absorption effect is slow is solved.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a breprazol dripping pill and a preparation method thereof. Background Art

[0002] Brepirapazole is the first dopamine D2, 5-HT1A receptor agonist and 5-HT2A receptor antagonist compound jointly developed by Otsuka Pharmaceutical Co., Ltd. of Japan and Lundbeck Pharma Ltd. of Denmark. It is a drug used to treat schizophrenia and major depressive disorder, and its dosage forms include tablets and orodisintegrating tablets.

[0003] Brapiprazol is a low-solubility drug, and the prepared Brapiprazol tablets have poor solubility and are not easy to dissolve. The Brapiprazol tablets in the prior art are prepared by wet granulation process, and then coated after tablet compression to obtain Brapiprazol tablets. The coating contains hydroxypropyl methylcellulose, talc, titanium dioxide and colorant, and the dissolution rate does not reach more than 85% in 15 minutes; and the orodisintegrating tablets have the disadvantages of being fragile and easy to absorb moisture, which increases the difficulty of packaging and transportation, and greatly affects the application of Brapiprazol orodisintegrating tablets. Psychiatric patients are prone to refuse to take medicine during medication treatment, and some patients have swallowing difficulties, especially the elderly and children.

[0004] In view of this, the present invention is proposed. Summary of the invention

[0005] One of the purposes of the present invention is to provide a brepizole dripping pill to solve the technical problem in the prior art that brepizole tablets or orally disintegrating tablets cannot be quickly dissolved, resulting in slow absorption and onset of effect.

[0006] The second object of the present invention is to provide a method for preparing the above-mentioned brepazole dropping pills.

[0007] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are particularly adopted:

[0008] In a first aspect, the present invention provides a brepirazole dropping pill, comprising brepirazole and a dropping pill matrix, wherein the weight ratio of the brepirazole to the dropping pill matrix is ​​10:138-356;

[0009] The drop pill matrix comprises polyethylene glycol, 70% acetic acid and poloxamer.

[0010] Furthermore, the composition comprises the following components in parts by weight: 10 parts of brepazole, 120-300 parts of polyethylene glycol, 12-26 parts of 70% acetic acid and 6-30 parts of poloxamer.

[0011] Furthermore, the polyethylene glycol is 180 to 300 parts by weight;

[0012] Preferably, the 70% acetic acid is 12 to 16 parts;

[0013] Preferably, the poloxamer is 6 to 10 parts.

[0014] Furthermore, the composition comprises the following components in parts by weight: 10 parts of brepazole, 180 parts of polyethylene glycol, 16 parts of 70% acetic acid and 10 parts of poloxamer.

[0015] Furthermore, the polyethylene glycol includes polyethylene glycol 4000 or polyethylene glycol 6000.

[0016] In a second aspect, the present invention provides a method for preparing the above-mentioned brepizole dropping pills, comprising adding 70% acetic acid dissolved with brepizole and poloxamer to polyethylene glycol under stirring according to the formula amount, stirring evenly and then dripping into a release agent to obtain brepizole dropping pills.

[0017] Furthermore, the preparation method of 70% acetic acid in which brepirazole and poloxamer are dissolved comprises adding brepirazole to 70% acetic acid under stirring, adding poloxamer after dissolution, and continuing to stir until dissolved.

[0018] Furthermore, before adding 70% acetic acid containing brepazole and poloxamer dissolved therein to polyethylene glycol, the process further comprises pre-heating the polyethylene glycol at 65° C. to 80° C. to maintain the polyethylene glycol in a molten state.

[0019] Furthermore, the stirring conditions include stirring at 65° C. to 80° C. for 10 to 18 minutes.

[0020] Furthermore, when preparing 70% acetic acid in which breprazol and poloxamer are dissolved, the stirring condition is stirring at 70° C. for 15 min;

[0021] Preferably, when 70% acetic acid in which brepirazole and poloxamer are dissolved is added to polyethylene glycol under stirring, the stirring condition is 70° C. for 10 min to 30 min.

[0022] The present invention provides a brepirazole drop pill, which uses 70% acetic acid as a solubilizing agent and promotes the dissolution of brepirazole and poloxamer under stirring conditions; uses poloxamer as a penetration enhancer to significantly improve the transdermal effect; uses polyethylene glycol to improve the water solubility of the drop pill; experiments show that when the weight ratio of brepirazole to the drop pill matrix is ​​within the range of 10:138-356, the hardness of the obtained spherical drop pill can be improved to the point that it can only be deformed by hand pressure; and the properties do not change significantly after being placed for 30 days, and have good stability; the 15min dissolution rate can reach 100%, which is better than the dissolution effect of tablets and orally disintegrating tablets in the prior art. Polyethylene glycol, 70% acetic acid and poloxamer as drop pill matrix can be combined with brepirazole to obtain spherical drop pills with sufficient hardness, stability and good dissolution rate. The technical problem that brepirazole tablets or orally disintegrating tablets in the prior art cannot be quickly dissolved, resulting in slow absorption and onset of effect is solved. DETAILED DESCRIPTION

[0023] Unless otherwise defined herein, scientific and technical terms used in conjunction with the present invention shall have the meanings commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear, however, in the case of any potential ambiguity, the definitions provided herein take precedence over any dictionary or external definitions. In this application, unless otherwise stated, the use of "or" means "and / or". In addition, the use of the term "including" and other forms is non-limiting.

[0024] The methods and techniques of the present invention are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated.

[0025] On one hand, the present invention provides a brepazine dropping pill, comprising brepazine and a dropping pill matrix, wherein the weight ratio of the brepazine to the dropping pill matrix is ​​10:138-356; the dropping pill matrix comprises polyethylene glycol, 70% acetic acid and poloxamer.

[0026] 70% acetic acid is used as a solubilizer and under stirring conditions to promote the dissolution of brepirazole and poloxamer; poloxamer is used as a penetration enhancer to significantly improve the transdermal effect; polyethylene glycol is used to improve the water solubility of the pellets; experiments have shown that when the weight ratio of brepirazole to the pellet matrix is ​​within the range of 10:138 to 356, the hardness of the obtained spherical pellets can be increased to the point where they can only be deformed by hand pressure; and there is no significant change in the properties after being placed for 30 days, and the pellets have good stability; the 15min dissolution rate can reach 100%, which is better than the dissolution effect of tablets and orally disintegrating tablets in the prior art. Polyethylene glycol, 70% acetic acid and poloxamer as the pellet matrix can be combined with brepirazole to obtain spherical pellets with sufficient hardness, stability and good dissolution rate. The technical problem that brepirazole tablets or orally disintegrating tablets in the prior art cannot be quickly dissolved, resulting in slow absorption and onset of effect, is solved.

[0027] The weight ratio of brepazole to the pill matrix may be, but is not limited to, 10:138, 10:158, 10:188, 10:208, 10:238, 10:258, 10:308, 10:338 or 10:356, or any ratio between 10:138 and 356.

[0028] In order to further improve the properties, hardness and raw material drug content of the pills, in some specific embodiments, the following components are included in weight: 10 parts of brepazole, 120-300 parts of polyethylene glycol, 12-26 parts of 70% acetic acid and 6-30 parts of poloxamer.

[0029] The weight proportion of the polyethylene glycol may be, but is not limited to, 120, 140, 160, 180, 200, 220, 240, 260, 280 or 300 parts, or any value between 120 and 300 parts.

[0030] The weight proportion of the 70% acetic acid may be, but is not limited to, 12, 14, 16, 18, 20, 22, 24 or 26 parts, and may be any value between 12 and 26 parts.

[0031] The weight proportion of the poloxamer may be, but is not limited to, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 or 30 parts, and may be any value between 6 and 30 parts.

[0032] Experiments have shown that when the amount of polyethylene glycol is 180 to 300 parts by weight, the content of the raw material drug is improved. In some specific embodiments, the amount of polyethylene glycol is 180 to 300 parts by weight.

[0033] The experiment found that when the dosage of 70% acetic acid was 26 parts, the content of the API did not increase. In some specific embodiments, the 70% acetic acid was 12 to 16 parts;

[0034] Experiments have shown that when the dosage of poloxamer is more than 10 parts, the content of the raw material drug is not further increased. In some specific embodiments, the poloxamer is 6 to 10 parts.

[0035] In some specific embodiments, the composition comprises the following components in parts by weight: 10 parts of brepizole, 180 parts of polyethylene glycol, 16 parts of 70% acetic acid and 10 parts of poloxamer.

[0036] In some specific embodiments, the polyethylene glycol comprises polyethylene glycol 4000 or polyethylene glycol 6000.

[0037] According to another aspect of the present invention, a method for preparing the above-mentioned brepirazole dropping pills is provided, comprising adding 70% acetic acid dissolved with brepirazole and poloxamer to polyethylene glycol under stirring according to the formula amount, stirring evenly and then dropping into a release agent to obtain brepirazole dropping pills.

[0038] The brepazol and poloxamer were first dissolved by using 70% acetic acid as a solubilizer to improve the dissolution effect of the raw materials, and then added to the polyethylene glycol matrix to improve the water solubility of the drop pills. The drop pills prepared by this method have good stability, hardness and water solubility.

[0039] In some specific embodiments, the method for preparing 70% acetic acid in which brepirazole and poloxamer are dissolved comprises adding brepirazole to 70% acetic acid under stirring, and then adding poloxamer after dissolution and continuing to stir until dissolved.

[0040] In some specific embodiments, before adding 70% acetic acid containing brepirazole and poloxamer dissolved therein to polyethylene glycol, the method further comprises pre-heating the polyethylene glycol at 65° C. to 80° C. to maintain the polyethylene glycol in a molten state.

[0041] In some specific embodiments, the stirring conditions include stirring at 65° C. to 80° C. for 10 to 18 min.

[0042] Specifically, when preparing 70% acetic acid in which brepazol and poloxamer are dissolved, the stirring condition is preferably stirring at 70°C for 15 minutes; when adding 70% acetic acid in which brepazol and poloxamer are dissolved into polyethylene glycol under stirring conditions, the stirring condition is preferably stirring at 70°C for 10 minutes to 30 minutes.

[0043] In the above method, the release agent can be dimethicone, white mineral oil, vegetable oil, stearic acid or silicone compounds, preferably dimethicone.

[0044] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0045] Example 1

[0046] A brepazole dripping pill comprises 1 mg of brepazole, 18 mg of polyethylene glycol 6000, 1.6 mg of 70% acetic acid and 1 mg of poloxamer.

[0047] The preparation is carried out according to the following steps: the prescribed amount of brepirazole is added to the acetic acid solution under stirring conditions, and the stirring conditions are 70°C for 15 minutes until the brepirazole is completely dissolved, and then poloxamer is added, and stirring is continued for about 15 minutes until the poloxamer is completely dissolved. The obtained solution is slowly added to the molten PEG6000 kept at 70°C under stirring conditions at 70°C, and stirred for 10 minutes. The obtained solution is dripped into dimethyl silicone oil to obtain brepirazole dripping pills.

[0048] Example 2

[0049] The difference from Example 1 is that the amount of 70% acetic acid used is 1.2 mg, and other conditions remain unchanged.

[0050] Example 3

[0051] The difference from Example 1 is that the amount of 70% acetic acid used is 2.6 mg, and other conditions remain unchanged.

[0052] Example 4

[0053] The difference from Example 1 is that the amount of poloxamer used is 0.6 mg, and other conditions remain unchanged.

[0054] Example 5

[0055] The difference from Example 1 is that the amount of poloxamer used is 2.0 mg, and other conditions remain unchanged.

[0056] Example 6

[0057] The difference from Example 1 is that the amount of poloxamer used is 3.0 mg, and other conditions remain unchanged.

[0058] Example 7

[0059] The difference from Example 1 is that the amount of polyethylene glycol 6000 used is 30 mg, and other conditions remain unchanged.

[0060] Example 8

[0061] The difference from Example 1 is that the amount of polyethylene glycol 6000 used is 12 mg, and other conditions remain unchanged.

[0062] Example 9

[0063] The difference from Example 1 is that polyethylene glycol 4000 is used instead of polyethylene glycol 6000, and other conditions remain unchanged.

[0064] Example 10

[0065] Different from Example 1, the preparation is carried out according to the following steps: the prescribed amount of brepirazole is added to the acetic acid solution under stirring conditions, and the stirring conditions are 65°C for 15 minutes until the brepirazole is completely dissolved, and then poloxamer is added, and stirring is continued for about 15 minutes until the poloxamer is completely dissolved. The obtained solution is slowly added to the molten PEG4000 kept at 65°C under stirring conditions at 65°C, and stirred for 30 minutes. The obtained solution is dripped into dimethyl silicone oil to obtain brepirazole dripping pills.

[0066] Embodiment 11

[0067] Different from Example 1, the preparation is carried out according to the following steps: the prescribed amount of brepirazole is added to the acetic acid solution under stirring conditions, and the stirring conditions are 80°C for 15 minutes until the brepirazole is completely dissolved, and then poloxamer is added, and stirring is continued for about 15 minutes until the poloxamer is completely dissolved. The obtained solution is slowly added to the molten PEG6000 kept at 80°C under stirring conditions at 80°C, and stirred for 10 minutes. The obtained solution is dripped into dimethyl silicone oil to obtain brepirazole dripping pills.

[0068] Comparative Example 1

[0069] The difference from Example 1 is that 2.2 mg of 50% citric acid is used instead of 1.6 mg of 70% acetic acid, and other conditions remain unchanged.

[0070] Comparative Example 2

[0071] The difference from Example 1 is that 3.1 mg of concentrated hydrochloric acid is used instead of 1.6 mg of 70% acetic acid, and other conditions remain unchanged.

[0072] Comparative Example 3

[0073] The difference from Example 1 is that 3.7 mg of 30% acetic acid is used instead of 1.6 mg of 70% acetic acid, and other conditions remain unchanged.

[0074] Comparative Example 4

[0075] The difference from Example 1 is that 2.2 mg of 50% acetic acid is used instead of 1.6 mg of 70% acetic acid, and other conditions remain unchanged.

[0076] Comparative Example 5

[0077] The difference from Example 1 is that 1.2 mg of 100% acetic acid is used instead of 1.6 mg of 70% acetic acid, and other conditions remain unchanged.

[0078] Comparative Example 6

[0079] Different from Example 1, 70% acetic acid was not added.

[0080] The preparation is carried out according to the following steps: the prescribed amount of brepazole is slowly added to the molten PEG4000 kept at 70°C under stirring conditions, stirred for 10 minutes, and then poloxamer is added and stirred for 20 minutes. The obtained approximate solution is dripped into dimethyl siphonic oil to obtain brepazole dripping pills.

[0081] Comparative Example 7

[0082] The difference from Example 1 is that 1 mg of caprylic acid macrogol glyceride is used instead of 1 mg of poloxamer, and other conditions remain unchanged.

[0083] Comparative Example 8

[0084] The difference from Example 1 is that 1 mg of mono- and di-caprylic caprylic glyceride is used instead of 1 mg of poloxamer, and other conditions remain unchanged.

[0085] Comparative Example 9

[0086] Different from Example 1, no poloxamer was added.

[0087] The preparation is carried out according to the following steps: the prescribed amount of brepazole is added to the acetic acid solution under stirring conditions, and the stirring conditions are 70°C for 15 minutes until the brepazole is completely dissolved. The obtained solution is slowly added to the molten PEG4000 kept at 70°C under stirring conditions at 70°C, and stirred for 20 minutes. The obtained solution is dripped into dimethyl silicone oil to obtain brepazole dripping pills.

[0088] Experiment 1: Testing of properties, hardness and stability of pills

[0089] 1. Observe and record the appearance and color of the breprazol dripping pills of Examples 1 to 11 and Comparative Examples 1 to 9.

[0090] 2. The hardness of the breprazol dropping pills of Examples 1 to 11 and Comparative Examples 1 to 9 was compared by hand pressure. When the shape of the dropping pill changed when the thumb and index finger pressed lightly, it was deformable by light pressure; when the shape of the dropping pill changed when the thumb and index finger pressed down with a rolling force, it was deformable by strong pressure; if the shape of the dropping pill did not change, it was basically not deformed by strong pressure.

[0091] 3. The brepazine dropping pills of Examples 1 to 11 and Comparative Examples 1 to 9 were placed for 30 days, and the changes of the dropping pills were observed during this period.

[0092] 4. The brepirazole content in the brepirazole dropping pills of Examples 1 to 11 and Comparative Examples 1 to 9 was detected by using HPLC method.

[0093] The above test results are shown in Table 1.

[0094] Table 1 Properties, hardness and stability test results of different breprazol dropping pills

[0095]

[0096]

[0097] As shown in Table 1, in combination with Examples 1 to 3 and Comparative Examples 1 to 6, it can be seen that using 30% acetic acid, citric acid or concentrated hydrochloric acid instead of acetic acid cannot obtain spherical dropping pills, and the hardness is low; although spherical dropping pills can be obtained using 50% acetic acid, the hardness is still lower than that of Examples 1 to 3; when 100% acetic acid is used, the hardness is higher than that of Examples 1 to 3, but the raw material drug (brepazole) precipitates after being placed for 4 days, and the stability is poor; if acetic acid is not added, the content of the raw material drug is affected. Therefore, 70% acetic acid is the best.

[0098] In combination with Example 1, Examples 4 to 6 and Comparative Examples 7 to 9, it can be seen that although spherical pellets can be obtained by using caprylic acid caprylic acid polyethylene glycol glyceride or mono- and di-caprylic acid capric acid glyceride, or without adding any penetration enhancer, the hardness and stability are lower than those in the examples; Example 1 and Examples 4 to 6 show good properties, hardness and stability.

[0099] Combining Example 1 with Examples 7 to 9, it can be seen that PEG4000 and PEG6000 can both be used as the matrix.

[0100] In combination with Example 1, Example 10 and Example 11, it can be known that qualified brexpiprazole dripping pills can be prepared at 65°C to 80°C.

[0101] Experiment 2: Transdermal detection

[0102] The brepazine dripping pills of Examples 1 to 6, Comparative Example 4, Comparative Example 5 and Comparative Examples 7 to 9 were tested using the intelligent transdermal tester TP-6 ​​under the following conditions, and a 2 mg / tablet orally disintegrating tablet (Otsuka Pharmaceutical Co., Ltd., Japan) commercially available in the prior art was used as a comparison.

[0103] Dissolution medium: pH 5.0 citrate-phosphate buffer.

[0104] Preparation of pH 5.0 citric acid-phosphate buffer: Take 17.91g of disodium hydrogen phosphate dodecahydrate, add degassed purified water to dissolve and dilute to 1000ml, stir evenly, and obtain 0.05mol / L disodium hydrogen phosphate solution. Take 5.25g of citric acid monohydrate, add degassed purified water to dissolve and dilute to 1000ml, stir evenly, and obtain 0.025mol / L citric acid solution. Take 0.05mol / L disodium hydrogen phosphate solution, adjust the pH value to 5.0±0.05 with 0.025mol / L citric acid solution, stir evenly, and obtain pH 5.0 citric acid-phosphate buffer.

[0105] Follow the steps below: add the dissolution medium to the vertical absorption pool, place the release membrane soaked in the dissolution medium for more than 30 minutes at the mouth of the receiving chamber, place the silicone gasket (2 mm) on the release membrane, clamp the upper and lower parts of the receiving chamber with a clip, place it on the transdermal instrument, and place the dripping pill equivalent to 2 mg of brepazine on the release membrane. Place 4 more vertical absorption pools in the same way, and take samples at 5 minutes, 10 minutes, 15 minutes, and 20 minutes respectively.

[0106] The chromatographic conditions were as follows:

[0107] Chromatographic column: Octadecylsilane bonded silica as filler (Inertsil ODS-3, 4.6×250mm, 5μm or InfinityLab Poroshell 120EC-C18 4.6×100mm, 2.7μm or other chromatographic columns with equivalent performance);

[0108] Mobile phase: 0.01 mol / L potassium dihydrogen phosphate solution (pH adjusted to 2.3 with phosphoric acid)-acetonitrile (65:35);

[0109] Flow rate: 1.0ml / min;

[0110] Detection wavelength: 323nm;

[0111] Column temperature: 40°C;

[0112] Injection volume: 5 μl.

[0113] The specific results are shown in Table 2.

[0114] Table 2 Cumulative dissolution in pH 5.0 medium (%)

[0115]

[0116]

[0117] As shown in Table 2, the dissolution rates of Examples 1 to 6 are all higher than that of the orally disintegrating tablet.

[0118] Combining the dissolution rates of Examples 1 to 3, Comparative Example 4, Comparative Example 5 and orally disintegrating tablets, it can be seen that the dissolution rate of the brepizole dripping pills with 70% acetic acid as a solubilizer is higher than that of the brepizole dripping pills with 100% acetic acid as a solubilizer at 15 min, and higher than that of the brepizole dripping pills with 50% acetic acid as a solubilizer at 20 min, and is significantly higher than that of the orally disintegrating tablets.

[0119] Combining the dissolution of Example 1, Examples 4 to 6 and Comparative Examples 7 to 9, it can be seen that the dissolution of the brepirazole drop pills using poloxamer as a penetration enhancer is better than that of the brepirazole drop pills using caprylic acid caprylic acid macrogol glyceride or mono- and di-caprylic acid capric acid glyceride as a penetration enhancer. The dissolution of the brepirazole drop pills without adding poloxamer is close to 0 at 5 minutes, which shows that adding poloxamer can improve the permeability of the drop pills.

[0120] Experiment 3 pH 4.3 medium dissolution test

[0121] The dissolution test of the brepazine dripping pills of Examples 1 to 6 and Comparative Examples 4 to 9 was carried out in a pH 4.3 medium. The operation was specifically carried out according to the following steps:

[0122] The specific test results are shown in Table 3.

[0123] Table 3 Dissolution rate in pH 4.3 medium (%)

[0124]

[0125]

[0126] As shown in Table 3, combined with the dissolution rates of Examples 1 to 3, Comparative Examples 5 to 6 and orally disintegrating tablets, it can be seen that the dissolution rate of the brepirazole dripping pills with 70% acetic acid as a solubilizer reaches more than 97% at 15 minutes and 100% at 20 minutes. The brepirazole dripping pills with 100% acetic acid as a solubilizer are lower than those of the examples at 15 minutes and do not reach 100% at 20 minutes; the dissolution rate of the brepirazole dripping pills without adding acetic acid is significantly reduced; and the examples are all better than the orally disintegrating tablets. Therefore, 70% acetic acid can improve the dissolution rate of the brepirazole dripping pills.

[0127] In combination with Example 1, Examples 4 to 6 and Comparative Examples 7 to 9, it can be seen that the dissolution rate of the brepirazole drop pills using poloxamer as a penetration enhancer reached 100% at 15 minutes, which is significantly better than the dissolution rate of the brepirazole drop pills with caprylic acid caprylic acid macrogol glyceride or without adding poloxamer. Although the dissolution rate of the brepirazole drop pills with mono- and di-caprylic acid capric acid glyceride as a penetration enhancer is not significantly different from that of the examples, it can be seen from the data in Table 2 that the addition of poloxamer can not only improve the solubility of the drop pills, but also improve the dissolution rate.

[0128] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A breprazol dripping pill, characterized in that: It comprises brepazole and a pill matrix, wherein the weight ratio of brepazole to the pill matrix is ​​10:138-356; The drop pill matrix comprises polyethylene glycol, 70% acetic acid and poloxamer.

2. The breprazol dripping pill according to claim 1, characterized in that The invention comprises the following components in parts by weight: 10 parts of brepazole, 120-300 parts of polyethylene glycol, 12-26 parts of 70% acetic acid and 6-30 parts of poloxamer.

3. The breprazol dripping pill according to claim 2, characterized in that: The polyethylene glycol is 180 to 300 parts by weight; Preferably, the 70% acetic acid is 12 to 16 parts; Preferably, the poloxamer is 6 to 10 parts.

4. The breprazol dripping pill according to claim 2, characterized in that: The invention comprises the following components in parts by weight: 10 parts of brepizole, 180 parts of polyethylene glycol, 16 parts of 70% acetic acid and 10 parts of poloxamer.

5. The breprazol dripping pill according to any one of claims 1 to 4, characterized in that: The polyethylene glycol includes polyethylene glycol 4000 or polyethylene glycol 6000.

6. The method for preparing the breprazol dripping pills according to any one of claims 1 to 5, characterized in that: The method comprises adding 70% acetic acid in which brepirazole and poloxamer are dissolved into polyethylene glycol under stirring according to the formula amount, and then dripping the mixture into a release agent after stirring evenly to obtain brepirazole dripping pills.

7. The preparation method according to claim 6, characterized in that: The preparation method of 70% acetic acid in which brepirazole and poloxamer are dissolved comprises the steps of adding brepirazole to 70% acetic acid under stirring, adding poloxamer after the brepirazole is dissolved, and continuing to stir until the poloxamer is dissolved.

8. The preparation method according to claim 6, characterized in that: Before adding 70% acetic acid containing brepazole and poloxamer dissolved therein to polyethylene glycol, the method further comprises preheating the polyethylene glycol at 65° C. to 80° C. to maintain the polyethylene glycol in a molten state.

9. The preparation method according to claim 6, characterized in that: The stirring conditions include stirring at 65° C. to 80° C. for 10 to 18 minutes.

10. The preparation method according to any one of claims 6 to 9, characterized in that: When preparing 70% acetic acid in which breprazol and poloxamer are dissolved, the stirring condition is stirring at 70° C. for 15 min; Preferably, when 70% acetic acid in which brepirazole and poloxamer are dissolved is added to polyethylene glycol under stirring, the stirring condition is 70° C. for 10 min to 30 min.

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