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Dihydroxynaphthoic acid galanthamine sustained-release particle for injection and preparation method thereof

A technology of galanthamine pamoate and slow-release microparticles, which is applied in the field of galanthamine pamoate sustained-release microparticles for injection and its preparation, and can solve unfavorable process scale-up applications, low adsorption, and parameter deviation And other issues

Pending Publication Date: 2021-09-14
LUNAN PHARMA GROUP CORPORATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The advantage of this method is that the particle size of the microspheres can be controlled intensively, but there are the following disadvantages: (1) The microsphere preparation process of the O / W emulsification-solvent evaporation method is suitable for the microsphere encapsulation of fat-soluble drugs
During the preparation process, the parameters are slightly deviated, which is prone to nozzle clogging, microspheres sticking together, etc., which adds a large degree of difficulty to the preparation process of microspheres, which is not conducive to the scale-up application of the process
[0005] Patent documents with application numbers 201811437827.3 and 201811437836.2 disclose a kind of galantamine pamoate; compared with galantamine hydrobromide, galantamine pamoate has the following advantages: significantly reducing solubility in water, relatively Low adsorption, good tablet formability, no bitterness, good stability, but has a certain hygroscopicity, and has not been used in the research and development of long-acting sustained-release injections

Method used

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  • Dihydroxynaphthoic acid galanthamine sustained-release particle for injection and preparation method thereof
  • Dihydroxynaphthoic acid galanthamine sustained-release particle for injection and preparation method thereof
  • Dihydroxynaphthoic acid galanthamine sustained-release particle for injection and preparation method thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0026] The preparation method of galantamine pamoate:

[0027] Dissolve 1.14 g of galantamine hydrobromide in 25 mL of dimethyl sulfoxide, add dropwise 100 mL of a dimethyl sulfoxide solution containing 1.41 g of pamoic acid, and after the drop is complete, stir and react at 25°C for 6 hours; Cool to 0-5°C and stand at this temperature for 24 hours, vacuum filter, and vacuum-dry at 50°C for 12 hours to obtain a light yellow powder which is galanthamine pamoate with a yield of 78.55% and a purity of 99.91% . All other raw materials and reagents used are commercially available.

[0028] In the embodiment, taking PLGA (75 / 25, 45000) as an example, it refers to a lactide-glycolide copolymer with a molar ratio of lactide to glycolide of 75:25 and a molecular weight of 45000; carboxyl-terminated, Both ester-terminated and hydroxyl-terminated lactide-glycolide copolymers can achieve the purpose of the present invention, and carboxyl-terminated lactide-glycolide copolymers are used ...

Embodiment 1

[0030] prescription:

[0031] PLGA (75 / 25, 45000) 35.892g

[0032] Galantamine Pamoate 8.975g

[0033] Arginine 0.135g

[0034] Preparation steps:

[0035] a. Mixing: Weigh the prescribed amount of PLGA, galanthamine pamoate and arginine and add them to a three-dimensional mixer for mixing. The working frequency is 25Hz and the time is 15min to prepare the mixture;

[0036] b. Melting and extruding: Add the mixture obtained in step a to the hopper feeding zone of the melting extruder. The mixture is heated in the conveying zone and then transported to the mixing zone. The air bubbles mixed in the product are extruded in the extrusion zone to cool the extrudate;

[0037] The parameters of the twin-screw extruder are as follows:

[0038]

[0039] c. Pulverization: put the extrudate obtained in step b in a ball mill, freeze it with liquid nitrogen for 10 minutes, grind it at -15°C to -5°C at a low temperature, work at a frequency of 30Hz, and pass it through a sieve of -9...

Embodiment 2

[0042] prescription:

[0043] PLGA (75 / 25, 45000) 35.82g

[0044] Galantamine Pamoate 8.955g

[0045] Lysine 0.225g

[0046] Preparation steps:

[0047] a. Mixing: Weigh the prescribed amount of PLGA, galanthamine pamoate and lysine and add them to a three-dimensional mixer for mixing. The working frequency is 25Hz and the time is 15min to prepare the mixture;

[0048] b. Melting and extruding: Add the mixture obtained in step a to the hopper feeding zone of the melting extruder. The mixture is heated in the conveying zone and then transported to the mixing zone. The air bubbles mixed in the product are extruded in the extrusion zone to cool the extrudate;

[0049] The parameters of the twin-screw extruder are as follows:

[0050]

[0051]

[0052] c. Pulverization: put the extrudate obtained in step b in a ball mill, freeze it with liquid nitrogen for 10 minutes, grind it at -15°C to -5°C at a low temperature, work at a frequency of 30Hz, and pass it through a sieve ...

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Abstract

The invention discloses a pamoxamic acid galanthamine sustained-release particle for injection and a preparation method of the pamoxamic acid galanthamine sustained-release particle. The particles comprise galanthamine pamoate, a lactide-glycolide copolymer and a weakly alkaline additive, and then is prepared by adopting a hot melt extrusion combined low-temperature crushing technology. Compared with the prior art, the prepared microparticle is small in burst release, sufficient in drug release, low in moisture content, simple in preparation process, high in product yield and encapsulation efficiency and suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of drug sustained-release preparations, in particular to a galanthamine pamoate sustained-release microparticle for injection and a preparation method thereof. Background technique [0002] Alzheimer's disease (AD) is a progressive neurodegenerative disease of the elderly. In recent years, with the accelerated development of population aging, the incidence of AD has increased significantly. Galantamine is a second-generation competitive AchE inhibitor with high specificity for neuronal AchE. It was approved by the FDA in February 2001 for the treatment of mild to moderate AD patients and has become the first choice for the treatment of senile dementia. drug. [0003] Galantamine is unstable in the air and is usually prepared as hydrobromide. Due to its short biological half-life, the commercially available dosage forms are administered more frequently: Galantamine Hydrobromide Tablets (5mg, 4 times / Day), ...

Claims

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Application Information

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IPC IPC(8): A61K9/16A61K31/55A61K47/34A61P25/28
CPCA61K9/0019A61K9/1647A61K31/55A61P25/28A61K47/34A61K9/16
Inventor 张贵民杜丽平高西蒙刘忠
Owner LUNAN PHARMA GROUP CORPORATION
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