US-12622902-B2 - Anti-arrhythmic pharmaceutical composition and preparation method therefor

Abstract

An anti-arrhythmic pharmaceutical composition. The pharmaceutical composition includes: an active ingredient, including 1-(3-methanesulfonamido benzyl)-6-methoxy, 7-benzyloxy-1,2,3,4-tetrahydroisoquinoline or a pharmaceutically acceptable salt thereof; and auxiliary materials, including lactose, microcrystalline cellulose and a pre-gelatinized starch, which account for 30% to 80% of the total weight of the composition. The composition has a good dissolution effect and excellent stability, and can be better applied to clinic.

Inventors

• Wei Xiao
• Hui Zhang
• Qingming Guo
• Zhenzhong Wang
• Xiaolian HE
• Xuehong DONG
• Yanqiu Wang

Assignees

• JIANGSU KANION PHARMACEUTICAL CO., LTD.

Dates

Publication Date

20260512

Application Date

20210308

Priority Date

20200331

Claims (6)

1. 1 . A pharmaceutical composition for treating arrhythmia, comprising: 43.6 parts by weight of 1-(3-methanesulfonamido benzyl)-6-methoxy, 7-benzyloxy-1,2,3,4-tetrahydroisoquinoline phosphate, 13.2 parts by weight of lactose, 26.4 parts by weight of microcrystalline cellulose, 13.2 parts by weight of pre-gelatinized starch, 2.9 parts, of croscarmellose sodium and 0.7 parts of magnesium stearate.
2. 2 . The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a granule, tablet or capsule.
3. 3 . The pharmaceutical composition according to claim 1 , further comprising an adhesive, wherein: the adhesive is selected from at least one of hydroxypropyl methylcellulose, hydroxypropyl cellulose, carboxymethylcellulose sodium, polyvinylpyrrolidone and methylcellulose; and the adhesive content is 0.5%-10% of the total weight of the composition.
4. 4 . A method for preparing the pharmaceutical composition according to claim 1 , comprising: a) mixing and sieving an active ingredient, lactose, microcrystalline cellulose and a pre-gelatinized starch; b) performing wet granulation; c) performing dynamic drying; and d) performing granule arrangement and total mixing.
5. 5 . The method according to claim 4 , wherein when the pharmaceutical composition is selected from a tablet, the method comprises: weighing 43.6 parts by weight of 1-(3-methanesulfonamido benzyl)-6-methoxy, 7-benzyloxy-1,2,3,4-tetrahydroisoquinoline phosphate, 13.2 parts by weight of lactose, 26.4 parts by weight of microcrystalline cellulose and 13.2 parts by weight of pre-gelatinized starch, mixing the materials uniformly and sieving the materials with a 80-mesh sieve; adding a 75% ethanol solution with 3% hydroxypropyl methylcellulose to prepare a soft material, and sieving the material with a 20-mesh sieve for granulation; performing air-blowing drying at 50° C. by using a hot air circulation oven; performing granule arrangement by using a 20-mesh sieve; adding 2.9 parts of croscarmellose sodium and 0.7 parts of magnesium stearate into dry granules after granule arrangement; and tableting.
6. 6 . The pharmaceutical composition according to claim 3 , wherein the adhesive content is 1.25% of the total weight of the composition.

Description

TECHNICAL FIELD The present application belongs to the field of pharmaceutical preparations, and particularly relates to an anti-arrhythmic pharmaceutical composition and a preparation method thereof. BACKGROUND Sudden cardiac death (SCD) is one of the main causes of death from cardiovascular diseases. SCD will be caused if regular heart rhythm disappears due to the instability of cardiac electrophysiology. The most serious ones are persistent ventricular tachycardia and ventricular fibrillation. Patent ZL200710181295.7 discloses 1-(3-methanesulfonamido benzyl)-6-methoxy, 7-benzyloxy-1,2,3,4-tetrahydroisoquinoline (hereinafter referred to as compound A) or a salt thereof. The compound A is known to be a class III anti-arrhythmic drug, can prolong action potential duration, and is effective to ventricular tachycardia and ventricular fibrillation. SUMMARY An objective of the present application is to provide an anti-arrhythmic pharmaceutical composition with high stability and rapid dissolution, and a preparation method thereof. Specifically, the pharmaceutical composition provided by the present application includes: an active ingredient, including 1-(3-methanesulfonamido benzyl)-6-methoxy, 7-benzyloxy-1,2,3,4-tetrahydroisoquinoline or a pharmaceutically acceptable salt thereof; andauxiliary materials, including lactose, microcrystalline cellulose and a pre-gelatinized starch, which account for 30% to 80% of the total weight of the composition. Further, the lactose, the microcrystalline cellulose and the pre-gelatinized starch account for 40% to 60% of a total weight of the composition. Preferably, a weight ratio of the lactose to the microcrystalline cellulose to the pre-gelatinized starch is 1:(1.8-2.2):(0.9-1.1). Preferably, the weight ratio is 1:(1.9-2.1):(0.9-1.1). More preferably, the weight ratio is 1:2:1. Further, the pharmaceutical composition further includes a disintegrating agent, wherein the disintegrating agent is selected from at least one of carboxymethyl starch sodium, croscarmellose sodium, low-substituted hydroxypropyl cellulose and crospovidone. Further, the disintegrating agent content is 1%-30% of the total weight of the composition, preferably, 2%-20%, more preferably, 2.5%-4%. Further, the pharmaceutical composition further includes a lubricant, wherein the lubricant is selected from at least one of magnesium stearate, zinc stearate, glyceryl behenate, sodium lauryl sulfate, hydrogenated vegetable oil, superfine silica powder, talcum powder and colloidal silicon dioxide, preferably, at least one of magnesium stearate and colloidal silicon dioxide. Specifically, the lubricant content is 0.5%-5% of the total weight of the composition, preferably, 0.7%. Specifically, the pharmaceutical composition may be a granule, tablet or capsule obtained after the active ingredient and the auxiliary materials are subjected to mixing granulation and drying processes. Further, the active ingredient content is 5%-70% of the total weight of the composition, preferably, 10%-50%, more preferably, 20%-45%. When the pharmaceutical composition is a tablet, the specific weight of the active ingredient content per tablet is 0.1-1000 mg, preferably, 10-500 mg, more preferably, 50-300 mg, further preferably, 100 mg. Further, the pharmaceutically acceptable salt may be hydrochloride or phosphate. Further, the pharmaceutical composition further includes an adhesive, wherein the adhesive is selected from at least one of hydroxypropyl methylcellulose, hydroxypropyl cellulose, carboxymethylcellulose sodium, polyvinylpyrrolidone and methylcellulose; and the adhesive content is 0.5%-10% of the total weight of the composition, preferably, 0.9%. More preferably, the prescription weight ratio of the pharmaceutical composition is as follows: IngredientsDosageCompound B43.6Lactose13.2Microcrystalline cellulose26.4Pre-gelatinized starch13.2Croscarmellose sodium2.9 The compound B is phosphate of the compound A. The present application further provides an application of the pharmaceutical composition as described in any one of the above to anti-arrhythmic therapy. The present application further provides a method for preparing the pharmaceutical composition as described above. The method includes: a) mixing and sieving an active ingredient, lactose, microcrystalline cellulose and a pre-gelatinized starch;b) performing wet granulation;c) drying; andd) performing granulation arrangement and total mixing. Specifically, the drying adopts static drying or fluidized drying. Specifically, the granulation method adopts a high-speed shearing granulation method or a fluidized bed spray granulation method. Further, when the pharmaceutical composition is selected from a tablet, the method further includes: weighing 43.6 parts by weight of 1-(3-methanesulfonamido benzyl)-6-methoxy, 7-benzyloxy-1,2,3,4-tetrahydroisoquinoline phosphate, 13.2 parts by weight of lactose, 26.4 parts by weight of microcrystalline cellulose and 13.2 parts by weigh