CN-121971593-A - Lumbrokinase enteric-coated pellet with high acid resistance and preparation method thereof

Abstract

The invention discloses a lumbrokinase enteric-coated pellet with high acid resistance and a preparation method thereof, and relates to the technical field of pharmacy. The preparation method comprises the following steps of S1, mixing lumbrokinase dry powder with blank mixed powder to obtain lumbrokinase mixed powder, S2, mixing blank pellets with the particle size of 900-1400 mu m, an adhesive and the lumbrokinase mixed powder, carrying out medicine wrapping and drying to obtain medicine-containing pellets, and S3, carrying out enteric coating on the medicine-containing pellets, wherein the moisture content of the coated pellets is less than or equal to 8%. According to the invention, by controlling the particle size and the water content after coating, the acid resistance of the prepared lumbrukinase is more than 97%, the lumbrukinase is still higher than 90% after 6 months of acceleration, the stability is obviously improved, and the potency of the lumbrukinase is also more stable.

Inventors

• LUO XIAORONG
• CHEN YING
• Chen Kaka
• JIANG YULI
• PENG KE
• ZHONG ZHIJIAN
• ZHU MINGHUI
• XIAO JINFA
• Tu Yingjuan
• LI WENGUI
• LIU JINPING
• HU RUIQI

Assignees

• 华润江中药业股份有限公司

Dates

Publication Date

20260505

Application Date

20260202

Claims (10)

1. 1. The preparation method of the lumbrokinase enteric-coated pellet with high acid resistance is characterized by comprising the following steps of: S1, mixing lumbrokinase dry powder with blank mixed powder to obtain lumbrokinase mixed powder; s2, mixing blank pellets with the particle size of 900-1400 mu m, an adhesive and lumbrokinase mixed powder, wrapping, and drying to obtain drug-containing pellets; S3, enteric coating is carried out on the drug-containing pellets, and the moisture content of the coated pellets is less than or equal to 8 percent, thus obtaining the drug-containing pellets.
2. 2. The method according to claim 1, wherein in step S1, the blank mixed powder is at least one selected from starch, microcrystalline cellulose, dextrin, and talc.
3. 3. The preparation method according to claim 1, wherein in the step S1, the mass ratio of the lumbrokinase dry powder to the blank mixed powder is (0.5-0.6): 1.
4. 4. The method according to claim 1, wherein in step S2, the particle size is 900 to 1180 μm.
5. 5. The preparation method of claim 1, wherein in the step S2, the adhesive is at least one selected from the group consisting of sucrose syrup and fructose syrup, and the parameters of the wrapping are that the spraying pressure is 0.2-0.4MPa, and the rotating speed of a host machine is 70-120rpm.
6. 6. The preparation method according to claim 1, wherein in the step S2, the mass ratio of the blank pellets, the binder and the lumbrokinase mixed powder is (2-2.5): (1.2-1.6): 1.
7. 7. The preparation method according to claim 1, wherein in the step S3, the solid content of the coating material in the coating solution of the enteric coating is 18-22%, the solvent is water, and the coating material consists of methacrylic acid copolymer, talcum powder, triethyl citrate, sodium bicarbonate, colloidal silica and sodium dodecyl sulfate.
8. 8. The preparation method of the enteric coating according to claim 7, wherein the preparation method of the enteric coating liquid comprises the steps of mixing a coating material with water and sieving.
9. 9. The preparation method according to claim 1, wherein in the step S3, the parameters of the enteric coating are that the pellet temperature is 28-35 ℃, the air inlet temperature is 50-90 ℃, the spraying speed is 30-80rpm, the spraying pressure is 0.15-0.35 MPa, the host machine speed is 40-100rpm, and the mass of the coating liquid is 30-35% of the mass of the drug-containing pellets.
10. 10. The Gao Naisuan lumbrukinase enteric-coated pellets prepared by the preparation method of any one of claims 1 to 9.

Description

Lumbrokinase enteric-coated pellet with high acid resistance and preparation method thereof Technical Field The invention relates to the technical field of pharmacy, in particular to a lumbrokinase enteric-coated pellet with high acid resistance and a preparation method thereof. Background The lumbrukinase is a proteolytic enzyme extracted and separated from artificially cultured Eisenia foetida, has selective affinity with fibrinogen, can directly hydrolyze fibrinogen to generate soluble fibrinogen degradation products, reduces the fibrinogen content and prevents thrombosis, contains components of a plasminogen activator and plasmin, and can degrade insoluble fibrin by promoting the conversion of the plasminogen into the plasmin and can dissolve thrombus of early cerebral infarction. A large number of clinical researches show that lumbrokinase has the functions of strongly dissolving thrombus, inhibiting platelet aggregation, reducing fibrinogen and improving hypercoagulability before thrombus formation. Because lumbrukinase is a biochemical medicine, the lumbrukinase is easy to inactivate in gastric acid, the lumbrukinase is protected from being damaged by gastric acid, so that the lumbrukinase is released in intestinal tracts, one mode is to directly fill active ingredients into enteric hollow capsules, but gastric acid still can permeate into the capsules through interfaces and damaged parts of the capsules to damage the active ingredients, and the other mode is to form a layer of compact enteric coating through an enteric coating technology. Therefore, the dosage forms of lumbrokinase products currently marketed mainly comprise enteric capsules and enteric tablets. However, the prior lumbrukinase enteric-coated capsule has the common problems that the lumbrukinase enteric-coated capsule has unstable quality, is easy to be fragile after being stored and has low upper probability. The powder in the damaged capsule is easy to adhere to the surfaces of other intact capsules, and most of the powder can be removed by polishing, but the powder at the interface is difficult to remove, so that not only is a great deal of powder wasted, but also the pollution opportunity is increased, and the production period is prolonged. In addition, gastric acid may penetrate into the capsule at the interface to destroy the effective components and reduce the drug effect. These problems seriously affect the quality and the curative effect of lumbrokinase enteric capsules and cause a certain pollution to the environment. Therefore, the modern scientific technology is urgently needed to be applied, the production process of the lumbrokinase enteric capsule is improved, the product quality standard is perfected, the safe, effective and stable product is produced, the curative effect of lumbrokinase is fully exerted, and the lumbrokinase enteric capsule is better served for patients. The commonly used preparation method of the pellets comprises an extrusion spheronization method, a fluid bed tangential spraying method, a centrifugal granulation method and the like. The pellets are prepared by adopting an extrusion spheronization method or a fluidized bed tangential spraying method, so that the medicines are placed in a high-temperature high-humidity environment for a long time, and the curative effect of the medicines is easy to be reduced. The centrifugal granulation process is to produce round and homogeneous pellet with high sphericity, high medicine releasing homogeneity and easy control of operation temperature and water content. Chinese patent application CN102119928A discloses a preparation method of lumbrokinase enteric-coated pellets, which comprises the steps of washing fresh Eisenia foetida with purified water, preparing homogenate by a colloid mill, repeatedly freezing and thawing, heating, centrifuging at high speed to obtain supernatant, separating the supernatant by an anion exchange chromatographic column, eluting, concentrating, filtering to obtain lumbrokinase concentrate, mixing the concentrate with an adhesive, spraying the mixture on a blank pellet core to prepare pellets, coating the pellets with enteric-coated pellets, and sieving. Chinese patent application CN102961359A discloses an lumbrokinase enteric-coated pellet capsule and a preparation method thereof. The lumbrukinase is made into pellets by using a centrifugal granulation technology, and the pellets are coated by adopting a low-temperature film-forming enteric coating formula and filled into gastric-soluble capsules. Meanwhile, the invention also adopts a dry powder coating method, and the method has the advantages of short preparation time, high drug loading capacity, target pellets (20-30 meshes), high yield, smooth and round appearance and the like. The invention can dissolve and absorb the pellets in the small intestine, effectively avoid the lumbrokinase from being damaged by gastric acid and ensure the curative effect. The core of the techni