Galanthamine pamoate sustained-release microspheres for injection and preparation method thereof

A technology of galantamine pamoate and pamoic acid, which is applied in the field of drug sustained-release preparations, and can solve the problems of unfavorable process scale-up application, nozzle clogging, low drug loading and encapsulation efficiency, etc.

Active Publication Date: 2021-05-21
LUNAN PHARMA GROUP CORPORATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CN108721252A discloses a single emulsification-solvent volatilization method to prepare agolametine long-acting injection sustained-release microspheres, which contain agolametine and biodegradable lactide-glycolide polymer (PLGA), It can maintain the blood drug concentration above 5ng / ml for more than 30 days, but there are problems of low actual drug loading and encapsulation efficiency
The advantage of this method is that it can concentrate on controlling the particle size of the microspheres, but it has 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
Patent application numbers 201811437827.3 and 201811437836.2 disclose a kind of galantamine pamoate; compared with galantamine hydrobromide, galantamine pamoate shows unique advantages: significantly reduced Solubility in water, good hygroscopicity, low adsorption, good tablet formability, no bitterness, good stability, but it has not been used in the research and development of long-acting sustained-release injections

Method used

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  • Galanthamine pamoate sustained-release microspheres for injection and preparation method thereof
  • Galanthamine pamoate sustained-release microspheres for injection and preparation method thereof
  • Galanthamine pamoate sustained-release microspheres for injection and preparation method thereof

Examples

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Effect test

Embodiment 1～5

[0045] Examples 1-5: Preparation of microspheres with different theoretical drug loadings

[0046] Table 1. The formulations and preparation process parameters of microspheres with different drug loadings

[0047]

[0048] Preparation:

[0049] The PLGA and galanthamine pamoate were weighed respectively, stirred and dissolved in 4mL of benzyl alcohol-dichloromethane mixed solvent to prepare the continuous phase, the concentration of PLGA in the continuous phase was 300mg / mL. Weigh 6.400g of PVA and add it to 500mL water for injection (100°C), stir until dissolved, cool the PVA solution to 25°C, add water for injection to 800mL, and make 8mg / mL PVA solution to obtain the dispersed phase. Slowly add the continuous phase to the dispersed phase, and homogeneously emulsify at 3000rpm for 1min; after the emulsification is complete, turn on the mechanical stirring to evaporate the solvent, and stop stirring after 3h; filter and collect the microspheres in 800mL of poloxamer ethan...

Embodiment 6

[0052] Prescription and preparation process parameters:

[0053]

[0054] Preparation:

[0055] Weigh PLGA and galanthamine pamoate respectively according to the prescription amount, stir and dissolve in 4.8mL benzyl alcohol-dichloromethane mixed solvent to prepare a continuous phase, the concentration of PLGA in the continuous phase is 250mg / mL. Weigh 8.000g of PVA and add it to 500mL water for injection (100°C), stir until dissolved, cool the PVA solution to 25°C, add water for injection to 800mL, and make a 10mg / mL PVA solution to obtain a dispersed phase. Slowly add the continuous phase to the dispersed phase, and homogeneously emulsify at 2000rpm for 1min; after the emulsification is completed, turn on the mechanical stirring to evaporate the solvent, and stop stirring after 3h; filter and collect the microspheres in 800mL of poloxamer ethanol aqueous solution, continue to stir for 1h, and The resulting suspension was filtered through a -100 mesh to +600 mesh screen t...

Embodiment 7

[0058] Prescription and preparation process parameters:

[0059]

[0060]

[0061] Preparation:

[0062] Weigh PLGA and galantamine pamoate respectively according to the prescription amount, stir and dissolve in 6mL benzyl alcohol-ethyl acetate mixed solvent to prepare a continuous phase, the concentration of PLGA in the continuous phase is 200mg / mL. Weigh 24.000g of PVA and add it to 500mL water for injection (100°C), stir until dissolved, cool the PVA solution to 25°C, add water for injection to 800mL, and make a 20mg / mL PVA solution to obtain a dispersed phase. Slowly add the continuous phase to the dispersed phase, and homogeneously emulsify at 4000rpm for 1min; after the emulsification is complete, turn on mechanical stirring to evaporate the solvent, and stop stirring after 3h; filter and collect the microspheres in 800mL polysorbate 80 ethanol aqueous solution, continue stirring for 1h, and The resulting suspension was filtered through a -100 mesh to +600 mesh sc...

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Abstract

The invention belongs to the technical field of drug sustained-release preparations, and particularly discloses galanthamine pamoate sustained-release microspheres for injection and a prpearation method thereof. The microspheres are composed of galanthamine pamoate and a lactide-glycolide copolymer. The galanthamine pamoate sustained-release microspheres for injection are prepared by adopting a mixed solvent system intervened O / W single emulsification-solvent evaporation method, and the microspheres are good in form, uniform in particle size, unique in core-shell structure, high in drug loading capacity and encapsulation efficiency and controllable in release period, and can meet the clinical requirements of different administration periods; and the preparation method of the microspheres is simple and feasible, and meets the requirements of modern industrial large-scale production.

Description

technical field [0001] The invention belongs to the technical field of drug sustained-release preparations, and in particular relates to a sustained-release microsphere of galanthamine pamoate for injection and a preparation method of the sustained-release microsphere for injection. Background technique [0002] Galantamine was approved by the FDA in February 2001 for the treatment of mild to moderate Alzheimer's disease (ALzheimer's desease, AD) patients, and has become the drug of choice for the treatment of senile dementia. As a second-generation acetylcholinesterase (AchE) inhibitor, galantamine has high specificity and mainly acts on the catalytic site of AchE. Hydrogen bond, the double bond of the cyclohexene ring forms a p-p bond with Trp84 in AChE, thereby inhibiting AchE; (2) the modification of the N-terminal alkylation in the molecular structure is conducive to approaching the bottom of the catalytic site of AchE, Plays a very important role in AchE inhibition. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/50A61K9/52A61K47/34A61K31/55A61P25/28
CPCA61K9/0019A61K9/5031A61K31/55A61P25/28Y02A50/30
Inventor 杜丽平张丽
Owner LUNAN PHARMA GROUP CORPORATION
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